Sarcopenic Obesity: The Underlying Molecular Pathophysiology and Prospect Therapies
Abstract
BACKGROUND: Age contributes to body composition alteration, rises a common disorder in elderly known as sarcopenic obesity (SO), which is characterized by the combination of obesity (excess fat mass) and sarcopenia (reduced skeletal muscle mass) clinical form and function.
CONTENT: The primary cause of SO is insulin resistance. Glucose transporter 4 (GLUT4) dysfunction results in impaired fatty acids oxidation. Decreased muscle mass results in lower mitochondria number and volume. Both will increase oxidative stress. Together with altered myokines in SO, oxidative stress was promoted and lead to higher M1 macrophages and failure in autophagy. The pro-inflammatory condition and dysbiosis links SO to a variety of cardiometabolic conditions, including non-alcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. The mortality, comorbidities, cardiometabolic diseases, and disability or impairment of SO is higher compare to obesity or sarcopenia alone. Some treatments have been developed for SO including adequate dietary intake, vitamin D and antioxidant supplementation, and exercises.
SUMMARY: SO is more prevalent among the elderly and has a significant negative impact on their quality of life. Therefore, maintaining muscle mass and strength as well as preventing obesity should be the key goals of initiatives to support healthy aging.
KEYWORDS: aging, body composition, obesity, sarcopenia, skeletal muscle, metabolic syndrome
Full Text:
PDFReferences
Kreidieh D, Itani L, El Kassas G, El Masri D, Calugi S, Dalle Grave R, et al. Long-term lifestyle-modification programs for overweight and obesity management in the Arab States: Systematic review and meta-analysis. Curr Diabetes Rev. 2018; 14(6): 550-8, CrossRef.
Meiliana A, Wijaya A. Update on obesity: Induced inflammation to cause cardiometabolic diseases. Indones Biomed J. 2022; 14(2): 116-38, CrossRef.
Itani L, Calugi S, Dalle Grave R, Kreidieh D, El Kassas G, El Masri D, et al. The association between body mass index and health-related quality of life in treatment-seeking Arab adults with obesity. Med Sci. 2018; 6(1): 25, CrossRef.
Abdelaal M, le Roux CW, Docherty NG. Morbidity and mortality associated with obesity. Ann Transl Med. 2017; 5(7): 161, CrossRef.
GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017; 377(1): 13-27, CrossRef.
Malafarina V, Úriz-Otano F, Iniesta R, Gil-Guerrero L. Sarcopenia in the elderly: Diagnosis, physiopathology and treatment. Maturitas. 2012; 71(2): 109-14, CrossRef.
Zamboni M, Mazzali G, Fantin F, Rossi A, Di Francesco V. Sarcopenic obesity: A new category of obesity in the elderly. Nutr Metab Cardiovasc Dis. 2008; 18(5): 388-95, CrossRef.
El Ghoch M, Calugi S, Grave RD. Sarcopenic Obesity: Definition, Health Consequences and Clinical Management. Open Nutr J. 2018; 12(1): 70-3, CrossRef.
Batsis JA, Cook SB. Is the whole not greater than the sum of its parts? The case of sarcopenic obesity. Am J Clin Nutr. 2017; 106(1): 14-5, CrossRef.
Sakuma K, Yamaguchi A. Sarcopenic obesity and endocrinal adaptation with age. Int J Endocrinol. 2013; 2013: 204164, CrossRef.
Biolo G, Cederholm T, Muscaritoli M. Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: From sarcopenic obesity to cachexia. Clin Nutr. 2014; 33(5): 737-48, CrossRef.
Jensen GL, Hsiao PY. Obesity in older adults: Relationship to functional limitation. Curr Opin Clin Nutr Metab Care. 2010; 13(1): 46-51, CrossRef.
Barazzoni R, Bischoff SC, Boirie Y, Busetto L, Cederholm T, Dicker D, et al. Sarcopenic obesity: Time to meet the challenge. Clin Nutr. 2018; 37(6 Pt A): 1787-93, CrossRef.
Nezameddin R, Itani L, Kreidieh D, El Masri D, Tannir H, El Ghoch M. Understanding Sarcopenic Obesity in Terms of Definition and Health Consequences: A Clinical Review. Curr Diabetes Rev. 2020 Jan 9;16(9):957-61, CrossRef.
Aryana IGPS, Astika IN, Kuswardhani RAT, Putrawan IBP, Purnami NKR, Putra WG, et al. High myostatin serum related with high prevalence of sarcopenia among elderly population in Pedawa Village, Bali, Indonesia. Indones Biomed J. 2019; 11(3): 293-8, CrossRef.
Koliaki C, Liatis S, Dalamaga M, Kokkinos A. Sarcopenic obesity: Epidemiologic evidence, pathophysiology, and therapeutic perspectives. Curr Obes Rep. 2019; 8(4): 458-71, CrossRef.
Batsis JA, Villareal DT. Sarcopenic obesity in older adults: Aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. 2018; 14(9): 513-37, CrossRef.
Batsis JA, Barre LK, Mackenzie TA, Pratt SI, Lopez-Jimenez F, Bartels SJ. Variation in the prevalence of sarcopenia and sarcopenic obesity in older adults associated with different research definitions: dual-energy X-ray absorptiometry data from the National Health and Nutrition Examination Survey 1999-2004. J Am Geriatr Soc. 2013; 61(6): 974-80, CrossRef.
Cruz-Jentoft AJ, Kiesswetter E, Drey M, Sieber CC. Nutrition, frailty, and sarcopenia. Aging Clin Exp Res. 2017; 29(1): 43-8, CrossRef.
Donini LM, Busetto L, Bischoff SC, Cederholm T, Ballesteros-Pomar MD, Batsis JA, et al. Definition and diagnostic criteria for sarcopenic obesity: ESPEN and EASO Consensus Statement. Obes Facts. 2022; 15(3): 321-35, CrossRef.
Baumgartner RN. Body composition in healthy aging. Ann NY Acad Sci. 2000; 904(1): 437-48, CrossRef.
Davison KK, Ford ES, Cogswell ME, Dietz WH. Percentage of body fat and body mass index are associated with mobility limitations in people aged 70 and older from NHANES III. J Am Geriatr Soc. 2002; 50(11): 1802-9, CrossRef.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010; 39(4): 412-23, CrossRef.
Xie WQ, Xiao GL, Fan YB, He M, Lv S, Li YS. Sarcopenic obesity: Research advances in pathogenesis and diagnostic criteria. Aging Clin Exp Res. 2019; 33(2): 247-52, CrossRef.
Samuel VT, Shulman GI. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 2016; 126(1): 12-22, CrossRef.
Benziger CP, Roth GA, Moran AE. The global burden of disease study and the preventable burden of NCD. Glob Heart. 2016; 11(4): 393-7, CrossRef.
Kalyani RR, Corriere M, Ferrucci L. Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases. Lancet Diabetes Endocrinol. 2014; 2(10): 819-29, CrossRef.
Rolland Y, Lauwers-Cances V, Cristini C, Van Kan GA, Janssen I, Morley JE, et al. Difficulties with physical function associated with obesity, sarcopenia, and sarcopenic-obesity in community-dwelling elderly women: the EPIDOS (EPIDemiologie de l'OSteoporose) Study. Am J Clin Nutr. 2009; 89(6): 1895-900, CrossRef.
Gemmink A, Goodpaster BH, Schrauwen P, Hesselink MKC. Intramyocellular lipid droplets and insulin sensitivity, the human perspective. Biochim Biophys Acta. 2017; 1862(10): 1242-9, CrossRef.
Brøns C, Grunnet LG. Mechanisms in Endocrinology: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: A causal mechanism or an innocent bystander? Eur J Endocrinol. 2017; 176(2): R67-78, CrossRef.
Pol A, Gross SP, Parton RG. Biogenesis of the multifunctional lipid droplet: Lipids, proteins, and sites. J Cell Biol. 2014; 204(5): 635-46, CrossRef.
Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest. 2000; 106(2): 171-6, CrossRef.
Rivas DA, McDonald DJ, Rice NP, Haran PH, Dolnikowski GG, Fielding RA. Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity. Am J Physiol Regul Integr Comp Physiol. 2016; 310(7): R561-9, CrossRef.
Peters SJ, Samjoo IA, Devries MC, Stevic I, Robertshaw HA, Tarnopolsky MA. Perilipin family (PLIN) proteins in human skeletal muscle: the effect of sex, obesity, and endurance training. Appl Physiol Nutr Metab. 2012; 37(4): 724-35, CrossRef.
Bosma M, Sparks LM, Hooiveld GJ, Jorgensen JA, Houten SM, Schrauwen P, et al. Overexpression of PLIN5 in skeletal muscle promotes oxidative gene expression and intramyocellular lipid content without compromising insulin sensitivity. Biochim Biophys Acta. 2013; 1831(4): 844-52, CrossRef.
Harris LALS, Skinner JR, Shew TM, Pietka TA, Abumrad NA, Wolins NE. Perilipin 5-driven lipid droplet accumulation in skeletal muscle stimulates the expression of fibroblast growth factor 21. Diabetes. 2015; 64(8): 2757-68, CrossRef.
Conte M, Vasuri F, Bertaggia E, Armani A, Santoro A, Bellavista E, et al. Differential expression of perilipin 2 and 5 in human skeletal muscle during aging and their association with atrophy-related genes. Biogerontology. 2015; 16(3): 329-40, CrossRef.
Bosma M. Lipid droplet dynamics in skeletal muscle. Exp Cell Res. 2016; 340(2): 180-6, CrossRef.
Cho KA, Kang PB. PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome. Int J Mol Med. 2015; 36(3): 839-44, CrossRef.
Fitzgibbons TP, Czech MP. Emerging evidence for beneficial macrophage functions in atherosclerosis and obesity-induced insulin resistance. J Mol Med. 2016; 94(3): 267-75, CrossRef.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003; 112(12): 1796-808, CrossRef.
Bing C. Is interleukin-1β a culprit in macrophage-adipocyte crosstalk in obesity? Adipocyte. 2015; 4(2): 149-52, CrossRef.
Castoldi A, De Souza CN, Saraiva Câmara NO, Moraes-Vieira PM. The macrophage switch in obesity development. Front Immunol. 2016: 6: 637, CrossRef.
Kob R, Bollheimer LC, Bertsch T, Fellner C, Djukic M, Sieber CC, et al. Sarcopenic obesity: Molecular clues to a better understanding of its pathogenesis? Biogerontology. 2015; 16(1): 15-29, CrossRef.
Boura-Halfon S, Zick Y. Phosphorylation of IRS proteins, insulin action, and insulin resistance. Am J Physiol Endocrinol Metab. 2009; 296(4): 581-91, CrossRef.
Hong SH, Choi KM. Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences. Int J Mol Sci. 2020; 21(2): 494, CrossRef.
Hafizi Abu Bakar M, Kian Kai C, Wan Hassan WN, Sarmidi MR, Yaakob H, Zaman Huri H. Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: The roles of long chain fatty acids. Diabetes Metab Res Rev. 2015; 31(5): 453-75, CrossRef.
Stinkens R, Goossens GH, Jocken JWE, Blaak EE. Targeting fatty acid metabolism to improve glucose metabolism. Obes Rev. 2015; 16(9): 715-57, CrossRef.
Kalinkovich A, Livshits G. Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev. 2017; 35: 200-21, CrossRef.
Chung HS, Choi KM. Adipokines and myokines: A pivotal role in metabolic and cardiovascular disorders. Curr Med Chem 2018; 25(20): 2401-15, CrossRef.
Fischer CP, Plomgaard P, Hansen AK, Pilegaard H, Saltin B, Pedersen BK. Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle. Am J Physiol Endocrinol Metab. 2004 ;287(6): E1189-94, CrossRef.
Wolsk E, Mygind H, Grøndahl TS, Pedersen BK, Van Hall G. IL-6 selectively stimulates fat metabolism in human skeletal muscle. Am J Physiol Endocrinol Metab. 2010; 299(5): E832-40, CrossRef.
Ellingsgaard H, Hauselmann I, Schuler B, Habib AM, Baggio LL, Meier DT, et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011; 17(11): 1481-9, CrossRef.
Zamboni M, Rubele S, Rossi AP. Sarcopenia and obesity. Curr Opin Clin Nutr Metab Care. 2019; 22(1): 13-9, CrossRef.
Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012; 481(7382): 463-8, CrossRef.
Zhang Y, Li R, Meng Y, Li S, Donelan W, Zhao Y, et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2014; 63(2): 514-25, CrossRef.
Natalicchio A, Marrano N, Biondi G, Spagnuolo R, Labarbuta R, Porreca I, et al. The myokine irisin is released in response to saturated fatty acids and promotes pancreatic β-cell survival and insulin secretion. Diabetes. 2017; 66(11): 2849-56, CrossRef.
Zhou X, Li R, Liu X, Wang L, Hui P, Chan L, et al. ROCK1 reduces mitochondrial content and irisin production in muscle suppressing adipocyte browning and impairing insulin sensitivity. 2016; 6: 29669, CrossRef.
Kurdiova T, Balaz M, Vician M, Maderova D, Vlcek M, Valkovic L, et al. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: In vivo and in vitro studies. J Physiol. 2014; 592(5): 1091-107, CrossRef.
Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002; 8(11): 1288-95, CrossRef.
Kang SY, Lim GE, Kim YK, Kim HW, Lee K, Park TJ, et al. Association between sarcopenic obesity and metabolic syndrome in postmenopausal women: A cross-sectional study based on the Korean National Health and Nutritional Examination Surveys from 2008 to 2011. J Bone Metab. 2017; 24(1): 9-14, CrossRef.
Lim S, Kim JH, Yoon JW, Kang SM, Choi SH, Park YJ, et al. Sarcopenic obesity: Prevalence and association with metabolic syndrome in the Korean Longitudinal Study on Health and Aging (KLoSHA). Diabetes Care. 2010; 33(7): 1652-4, CrossRef.
Lee J, Hong YP, Shin HJ, Lee W. Associations of sarcopenia and sarcopenic obesity with metabolic syndrome considering both muscle mass and muscle strength. J Prev Med Public Health. 2015; 49(1): 35-44, CrossRef.
Scott D, Cumming R, Naganathan V, Blyth F, Le Couteur DG, Handelsman DJ, et al. Associations of sarcopenic obesity with the metabolic syndrome and insulin resistance over five years in older men: The Concord Health and Ageing in Men Project. Exp Gerontol. 2018; 108: 99-105, CrossRef.
Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005; 115(5): 1343-51, CrossRef.
Kim JK, Michael MD, Previs SF, Peroni OD, Mauvais-Jarvis F, Neschen S, et al. Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle. J Clin Invest. 2000; 105(12): 1791-7, CrossRef.
Kim JK, Zisman A, Fillmore JJ, Peroni OD, Kotani K, Perret P, et al. Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. J Clin Invest; 108(1): 153-60, CrossRef.
Atkins JL, Wannamathee SG. Sarcopenic obesity in ageing: Cardiovascular outcomes and mortality. Br J Nutr. 2020; 124(10): 1102-13, CrossRef.
Semadhi MP, Barliana MI, Muliaty D, Wijaya A. Correlation of moderate-intensity physical exercise on irisin, oxidized-low-density lipoproteins and high-density lipoproteins cholesterol level in over 50 years old obese men. Indones Biomed J. 2019; 11(3): 257-61, CrossRef.
Walsh MC, Hunter GR, Livingstone MB. Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporos Int. 2006; 17(1): 61-7, CrossRef.
Griffiths RD. Muscle mass, survival, and the elderly ICU patient. Nutrition. 1996; 12(6): 456-8, CrossRef.
Cleasby ME, Jamieson PM, Atherton PJ. Insulin resistance and sarcopenia: mechanistic links between common co-morbidities. J Endocrinol. 2016; 229(2): R67-81, CrossRef.
Tilg H, Moschen AR. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006; 6(10): 772-83, CrossRef.
Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005; 115(5): 1111-9, CrossRef.
Lim JP, Leung BP, Ding YY, Tay L, Ismail NH, Yeo A, et al. Monocyte chemoattractant protein-1: A Proinflammatory cytokine elevated in sarcopenic obesity. Clin Interv Aging. 2015; 10: 605-9, CrossRef.
Yan QW, Yang Q, Mody N, Graham TE, Hsu CH, Xu Z, et al. The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes. 2007; 56(10): 2533-40, CrossRef.
Preissner KT. Adipose tissue-derived PAI-1: A molecular link for thrombo-inflammatory disease states? Thromb Haemost. 2012; 108(3): 415, CrossRef.
Das DK, Graham ZA, Cardozo CP. Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives. Acta Physiol. 2020; 228(2): e13367, CrossRef.
Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L. Sarcopenic obesity: Definition, cause and consequences. Curr Opin Clin Nutr Metab Care. 2008; 11(6): 693-700, CrossRef.
Havekes B, Sauerwein HP. Adipocyte-myocyte crosstalk in skeletal muscle insulin resistance; is there a role for thyroid hormone? Curr Opin Clin Nutr Metab Care. 2010; 13(6): 641-6, CrossRef.
Trayhurn P, Drevon CA, Eckel J. Secreted proteins from adipose tissue and skeletal muscle - adipokines, myokines and adipose/muscle cross-talk. Arch Physiol Biochem. 2011; 117(2): 47-56, CrossRef.
Rubio-Ruiz ME, Guarner-Lans V, Pérez-Torres I, Soto ME. Mechanisms underlying metabolic syndrome-related sarcopenia and possible therapeutic measures. Int J Mol Sci. 2019; 20(3): 647, CrossRef.
Pedersen BK. Muscles and their myokines. J Exp Biol. 2011; 214(Pt 2): 337-46, CrossRef.
Pedersen BK, Febbraio MA. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012; 8(8): 457-65, CrossRef.
Aryana IGPS, Winangun IMA. Decreased follistatin levels as a risk of acute sarcopenia marker in elderly. Mol Cell Biomed Sci. 2023; 7(3): 147-54, CrossRef.
Atkins JL, Whincup PH, Morris RW, Lennon LT, Papacosta O, Wannamethee SG. Sarcopenic obesity and risk of cardiovascular disease and mortality: A population-based cohort study of older men. J Am Geriatr Soc. 2014; 62(2): 253-60, CrossRef.
Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L. Sarcopenic obesity: Definition, cause and consequences. Curr Opin Clin Nutr Metab Care. 2008; 11(6): 693-700, CrossRef.
Kohara K. Sarcopenic obesity in aging population: Current status and future directions for research. Endocrine. 2014; 45(1): 15-25, CrossRef.
Sainsbury A, Zhang L. Role of the arcuate nucleus of the hypothalamus in regulation of body weight during energy deficit. Mol Cell Endocrinol. 2010; 316(2): 109-19, CrossRef.
Ticinesi A, Nouvenne A, Cerundolo N, Catania P, Prati B, Tana C, et al. Gut microbiota, muscle mass and function in aging: A focus on physical frailty and sarcopenia. Nutrients. 2019; 11(7): 1633, CrossRef.
Livshits G, Kalinkovich A. Inflammaging as a common ground for the development and maintenance of sarcopenia, obesity, cardiomyopathy and dysbiosis. Ageing Res Rev. 2019; 56: 100980, CrossRef.
Picca A, Fanelli F, Calvani R, Mulè G, Pesce V, Sisto A, et al. Gut dysbiosis and muscle aging: Searching for novel targets against sarcopenia. Mediators Inflamm. 2018: 2018: 7026198, CrossRef.
Hiippala K, Jouhten H, Ronkainen A, Hartikainen A, Kainulainen V, Jalanka J, et al. The potential of gut commensals in reinforcing intestinal barrier function and alleviating inflammation. Nutrients. 2018; 10(8): 988, CrossRef.
Cancello R, Turroni S, Rampelli S, Cattaldo S, Candela M, Cattani L, et al. Effect of short-term dietary intervention and probiotic mix supplementation on the gut microbiota of elderly obese women. Nutrients. 2019; 11(12): 3011, CrossRef.
Oliphant K, Allen-Vercoe E. Macronutrient metabolism by the human gut microbiome: Major fermentation by-products and their impact on host health. Microbiome. 2019; 7(1): 91, CrossRef.
Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019; 16(8): 461-78, CrossRef.
Muscariello E, Nasti G, Siervo M, Di Maro M, Lapi D, D'Addio G, et al. Dietary protein intake in sarcopenic obese older women. Clin Interv Aging. 2016; 11: 133-40, CrossRef.
Fromentin G, Darcel N, Chaumontet C, Marsset-Baglieri A, Nadkarni N, Tomé D. Peripheral and central mechanisms involved in the control of food intake by dietary amino acids and proteins. Nutr Res Rev. 2012; 25(1): 29-39, CrossRef.
Van Der Klaauw AA, Keogh JM, Henning E, Trowse VM, Dhillo WS, Ghatei MA, et al. High protein intake stimulates postprandial GLP1 and PYY release. Obesity. 2013; 21(8): 1602-7, CrossRef.
Ojha U. Protein-induced satiation and the calcium-sensing receptor. Diabetes, Metabolic Syndrome and Obesity. 2018; 11: 45-51, CrossRef.
Bliss ES, Whiteside E. The gut-brain axis, the human gut microbiota and their integration in the development of obesity. Front Physiol. 2018; 9: 900, CrossRef.
Erdmann J, Lippl F, Schusdziarra V. Differential effect of protein and fat on plasma ghrelin levels in man. Regul Pept. 2003; 116(1-3): 101-7, CrossRef.
Shrestha YB, Wickwire K, Giraudo SQ. Direct effects of nutrients, acetylcholine, CCK, and insulin on ghrelin release from the isolated stomachs of rats. Peptides. 2009; 30(6): 1187-91, CrossRef.
Al Massadi O, Pardo M, Roca-Rivada A, Castelao C, Casanueva FF, Seoane LM. Macronutrients act directly on the stomach to regulate gastric ghrelin release. J Endocrinol Invest. 2010; 33(9): 599-602, CrossRef.
Mignone LE, Wu T, Horowitz M, Rayner CK. Whey protein: The "whey" forward for treatment of type 2 diabetes? World J Diabetes. 2015; 6(14): 1274-84, CrossRef.
Blouet C, Jo YH, Li X, Schwartz GJ. Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. J Neurosci. 2009; 29(26): 8302-11, CrossRef.
Leitão-Gonçalves R, Carvalho-Santos Z, Francisco AP, Fioreze GT, Anjos M, Baltazar C, et al. Commensal bacteria and essential amino acids control food choice behavior and reproduction. PLoS Biol. 2017; 15(4): e2000862, CrossRef.
Diether NE, Willing BP. Microbial fermentation of dietary protein: An important factor in diet−microbe−host interaction. Microorganisms. 2019; 7(1): 19, CrossRef.
Dai ZL, Wu G, Zhu WY. Amino acid metabolism in intestinal bacteria: Links between gut ecology and host health. Front Biosci. 2011; 16(5): 1768-86, CrossRef.
Neis EPJG, Dejong CHC, Rensen SS. The role of microbial amino acid metabolism in host metabolism. Nutrients. 2015; 7(4): 2930-46, CrossRef.
Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, et al. The long-term stability of the human gut microbiota. Science. 2013; 341(6141): 1237439, CrossRef.
Ticinesi A, Milani C, Lauretani F, Nouvenne A, Mancabelli L, Lugli GA, et al. Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients. Sci Rep. 2017; 7(1): 11102, CrossRef.
Lustgarten MS. The role of the gut microbiome on skeletal muscle mass and physical eunction: 2019 update. Front Physiol. 2019; 10: 1435, CrossRef.
Casati M, Ferri E, Azzolino D, Cesari M, Arosio B. Gut microbiota and physical frailty through the mediation of sarcopenia. Exp Gerontol. 2019; 124: 110639, CrossRef.
Steves CJ, Bird S, Williams FMK, Spector TD. The microbiome and musculoskeletal conditions of aging: A review of evidence for impact and potential therapeutics. J Bone Miner Res. 2016; 31(2): 261-9, CrossRef.
Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012; 487(7408): 477-81, CrossRef.
Ticinesi A, Lauretani F, Milani C, Nouvenne A, Tana C, Del Rio D, et al. Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia: Is there a gut-muscle axis? Nutrients. 2017; 9(12): 1303, CrossRef.
Qi YF, Goel R, Kim S, Richards EM, Carter CS, Pepine CJ, et al. Intestinal permeability biomarker zonulin is elevated in healthy aging. J Am Med Dir Assoc. 2017; 18(9): 810.e1-4, CrossRef.
Sovran B, Hugenholtz F, Elderman M, Van Beek AA, Graversen K, Huijskes M, et al. Age-associated impairment of the mucus barrier function is associated with profound changes in microbiota and immunity. Sci Rep. 2019; 9(1): 1437, CrossRef.
Portune KJ, Beaumont M, Davila AM, Tomé D, Blachier F, Sanz Y. Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin. Trends Food Sci Technol. 2016; 57: 213-32, CrossRef.
Blachier F, Beaumont M, Portune KJ, Steuer N, Lan A, Audebert M, et al. High-protein diets for weight management: Interactions with the intestinal microbiota and consequences for gut health. A position paper by the my new gut study group. Clin Nutr. 2019; 38(3): 1012-22, CrossRef.
Morowitz MJ, Carlisle EM, Alverdy JC. Contributions of intestinal bacteria to nutrition and metabolism in the critically ill. Surg Oncol Clin N. 2011; 91(4): 771-85, CrossRef.
Metges CC. Contribution of microbial amino acids to amino acid homeostasis of the host. J Nutr. 2000; 130(7): 1857S-64S, CrossRef.
Pesta DH, Samuel VT. A high-protein diet for reducing body fat: mechanisms and possible caveats. Nutr Metab. 2014; 11(1): 53, CrossRef.
Westerterp-Plantenga MS, Lemmens SG, Westerterp KR. Dietary protein - its role in satiety, energetics, weight loss and health. Br J Nutr. 2012; 108(S2): S105-12, CrossRef.
Davila AM, Blachier F, Gotteland M, Andriamihaja M, Benetti PH, Sanz Y, et al. Intestinal luminal nitrogen metabolism: Role of the gut microbiota and consequences for the host. Pharmacol Res. 2013; 68(1): 95-107, CrossRef.
Windey K, de Preter V, Verbeke K. Relevance of protein fermentation to gut health. Mol Nutr Food Res. 2012; 56(1): 184-96, CrossRef.
Russell WR, Gratz SW, Duncan SH, Holtrop G, Ince J, Scobbie L, et al. High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr. 2011; 93(5): 1062-72, CrossRef.
Lan A, Andriamihaja M, Blouin JM, Liu X, Descatoire V, Desclée de Maredsous C, et al. High-protein diet differently modifies intestinal goblet cell characteristics and mucosal cytokine expression in ileum and colon. J Nutr Biochem. 2015; 26(1): 91-8, CrossRef.
Tomova A, Bukovsky I, Rembert E, Yonas W, Alwarith J, Barnard ND, et al. The effects of vegetarian and vegan diets on gut microbiota. Front Nutr. 2019; 6: 47, CrossRef.
Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013; 500(7464): 585-8, CrossRef.
Reichardt N, Duncan SH, Young P, Belenguer A, Mcwilliam Leitch C, Scott KP, et al. Erratum: Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 2014; 8(6): 1352, CrossRef.
Zhou XL, Yan BB, Xiao Y, Zhou YM, Liu TY. Tartary buckwheat protein prevented dyslipidemia in high-fat diet-fed mice associated with gut microbiota changes. Food Chem Toxicol. 2018; 119: 296-301, CrossRef.
Nakatani A, Li X, Miyamoto J, Igarashi M, Watanabe H, Sutou A, et al. Dietary mung bean protein reduces high-fat diet-induced weight gain by modulating host bile acid metabolism in a gut microbiota-dependent manner. Biochem Biophys Res Commun. 2018; 501(4): 955-61, CrossRef.
Yu H, Guo Z, Shen S, Shan W. Effects of taurine on gut microbiota and metabolism in mice. Amino Acids. 2016; 48(7): 1601-17, CrossRef.
Moreno-Pérez D, Bressa C, Bailén M, Hamed-Bousdar S, Naclerio F, Carmona M, et al. Effect of a protein supplement on the gut microbiota of endurance athletes: A randomized, controlled, double-blind pilot study. Nutrients. 2018; 10(3): 337, CrossRef.
Kim CH, Park J, Kim M. Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw. 2014; 14(6): 277-88, CrossRef.
Park JS, Lee EJ, Lee JC, Kim WK, Kim HS. Anti-inflammatory effects of short chain fatty acids in IFN-γ-stimulated RAW 264.7 murine macrophage cells: Involvement of NF-κB and ERK signaling pathways. Int Immunopharmacol. 2007; 7(1): 70-7, CrossRef.
Petropoulou K, Chambers ES, Morrison DJ, Preston T, Godsland IF, Wilde P, et al. Identifying crop variants with high resistant starch content to maintain healthy glucose homeostasis. Nutr Bull. 2016; 41(4): 372-7, CrossRef.
Chambers ES, Byrne CS, Morrison DJ, Murphy KG, Preston T, Tedford C, et al. Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: a randomised cross-over trial. Gut. 2019; 68(8): 1430-8, CrossRef.
Larsen N, Vogensen FK, Van Den Berg FWJ, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 2010; 5(2): e9085, CrossRef.
Karlsson FH, Tremaroli V, Nookaew I, Bergström G, Behre CJ, Fagerberg B, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013; 498(7452): 99-103, CrossRef.
Shen Z, Zhu C, Quan Y, Yang J, Yuan W, Yang Z, et al. Insights into Roseburia intestinalis which alleviates experimental colitis pathology by inducing anti-inflammatory responses. J Gastroenterol Hepatol. 2018; 33(10): 1751-60, CrossRef.
Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19(5): 576-85, CrossRef.
Dumas ME, Rothwell AR, Hoyles L, Aranias T, Chilloux J, Calderari S, et al. Microbial-host co-metabolites are prodromal markers predicting phenotypic heterogeneity in behavior, obesity, and impaired glucose tolerance. Cell Rep. 2017; 20(1): 136-48, CrossRef.
Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, et al. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol Nutr Food Res. 2017; 61(1): 1600324, CrossRef.
Landfald B, Valeur J, Berstad A, Raa J. Microbial trimethylamine-N-oxide as a disease marker: something fishy? Microb Ecol Health Dis. 2017; 28(1): 1327309, CrossRef.
Prokopidis K, Cervo MM, Gandham A, Scott D. Impact of protein intake in older adults with sarcopenia and obesity: A gut microbiota perspective. Nutrients. 2020; 12(8): 2285, CrossRef.
Den Besten G, Van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013; 54(9): 2325-40, CrossRef.
Dhingra D, Michael M, Rajput H, Patil RT. Dietary fibre in foods: A review. J Food Sci Technol. 2012; 49(3): 255-66,
Gibson R, Eriksen R, Chambers E, Gao H, Aresu M, Heard A, et al. Intakes and food sources of dietary fibre and their associations with measures of body composition and inflammation in UK adults: Cross-sectional analysis of the airwave health monitoring study. Nutrients. 2019; 11(8): 1839, CrossRef.
Fayet-Moore F, Cassettari T, Tuck K, McConnell A, Petocz P. Dietary fibre intake in Australia. Paper I: Associations with demographic, socio-economic, and anthropometric factors. Nutrients. 201; 10(5): 599, CrossRef.
Harris HC, Edwards CA, Morrison DJ. Impact of glycosidic bond configuration on short chain fatty acid production from model fermentable carbohydrates by the human gut microbiota. Nutrients. 2017; 9(1): 26, CrossRef.
Chambers ES, Preston T, Frost G, Morrison DJ. Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health. Curr Nutr Rep. 2018; 7(4): 198-206, CrossRef.
Cox MA, Jackson J, Stanton M, Rojas-Triana A, Bober L, Laverty M, et al. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines. World J Gastroenterol. 2009; 15(44): 5549-57, CrossRef.
Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019; 15(5): 261-73, CrossRef.
Sukkar AH, Lett AM, Frost G, Chambers ES. Regulation of energy expenditure and substrate oxidation by short-chain fatty acids. J Endocrinol. 2019; 242(2): R1-8, CrossRef.
Frampton J, Murphy KG, Frost G, Chambers ES. Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function. Nat Metab. 2020; 2(9): 840-8, CrossRef.
Alamshah A, Spreckley E, Norton M, Kinsey-Jones JS, Amin A, Ramgulam A, et al. L-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents. Int J Obes. 2017; 41(11): 1693-701, CrossRef.
Amin A, Neophytou C, Thein S, Martin NM, Alamshah A, Spreckley E, et al. L-arginine increases postprandial circulating GLP-1 and PYY levels in humans. Obesity. 2018; 26(11): 1721-6, CrossRef.
Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SEK, et al. Targeted delivery of propionate to the human colon prevents body weight and intra-abdominal adipose tissue gain in overweight adults. Proc Nutr Soc. 2014; 73: E22, CrossRef.
Chimerel C, Emery E, Summers DK, Keyser U, Gribble FM, Reimann F. Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells. Cell Rep. 2014; 9(4): 1202-8, CrossRef.
Spreckley E, Murphy KG. The L-cell in nutritional sensing and the regulation of appetite. Front Nutr. 2015; 2: 23, CrossRef.
Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, et al. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe. 2014; 16(4): 495-503, CrossRef.
Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, et al. Erratum: Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015; 163(1): 258, CrossRef.
Norton M, Murphy KG. Targeting gastrointestinal nutrient sensing mechanisms to treat obesity. Curr Opin Pharmacol. 2017; 37: 16-23, CrossRef.
Dagbasi A, Lett AM, Murphy K, Frost G. Understanding the interplay between food structure, intestinal bacterial fermentation and appetite control. Proc Nutr Soc. 2020; 79(4): 514-30, CrossRef.
Byrne CS, Chambers ES, Alhabeeb H, Chhina N, Morrison DJ, Preston T, et al. Increased colonic propionate reduces anticipatory reward responses in the human striatum to high-energy foods. Am J Clin Nutr. 2016; 104(1): 5-14, CrossRef.
Yau YHC, Potenza MN. Stress and eating behaviors. Minerva Endocrinol. 2013; 38(3): 255-67, PMID.
Beaumont M, Portune KJ, Steuer N, Lan A, Cerrudo V, Audebert M, et al. Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans. Am J Clin Nutr. 2017; 106(4): 1005-19, CrossRef.
Kritchevsky SB, Beavers KM, Miller ME, Shea MK, Houston DK, Kitzman DW, et al. Intentional weight loss and all-cause mortality: a meta-analysis of randomized clinical trials. PLoS One. 2015; 10(3): e0121993, CrossRef.
Villareal DT, Apovian CM, Kushner RF, Klein S. Obesity in older adults: Technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am J Clin Nutr. 2005; 82(5): 923-34, CrossRef.
Villareal DT, Chode S, Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011; 364(13): 1218-29, CrossRef.
Villareal DT, Aguirre L, Gurney AB, Waters DL, Sinacore DR, Colombo E, et al. Aerobic or resistance exercise, or both, in dieting obese older adults. N Engl J Med. 2017; 376(20): 1943-55, CrossRef.
Batsis JA, Villareal DT. Sarcopenic obesity in older adults: Aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. 2018; 14(9): 513-37, CrossRef.
Lo JH, U KP, Yiu T, Ong MT, Lee WY. Sarcopenia: Current treatments and new regenerative therapeutic approaches. J Orthop Translat. 2020; 23: 38-52, CrossRef.
Juffer P, Jaspers RT, Lips P, Bakker AD, Klein-Nulend J. Expression of muscle anabolic and metabolic factors in mechanically loaded MLO-Y4 osteocytes. Am J Physiol Endocrinol Metab. 2012; 302(4): 389-95, CrossRef.
Kaji H. Linkage between muscle and bone: Common catabolic signals resulting in osteoporosis and sarcopenia. Curr Opin Clin Nutr Metab Care. 2013; 16(3): 272-7, CrossRef.
Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, et al. Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise. Cell Metab. 2016; 23(6): 1078-92, CrossRef.
Bori Z, Zhao Z, Koltai E, Fatouros IG, Jamurtas AZ, Douroudos II, et al. The effects of aging, physical training, and a single bout of exercise on mitochondrial protein expression in human skeletal muscle. Exp Gerontol. 2012; 47(6): 417-24, CrossRef.
Lanza IR, Nair KS. Muscle mitochondrial changes with aging and exercise. Am J Clin Nutr. 2009; 89(1): 467S-71S, CrossRef.
Barillaro C, Liperoti R, Martone AM, Onder G, Landi F. The new metabolic treatments for sarcopenia. Aging Clin Exp Res. 2013; 25(2): 119-27, CrossRef.
Trouwborst I, Verreijen A, Memelink R, Massanet P, Boirie Y, Weijs P, et al. Exercise and nutrition strategies to counteract sarcopenic obesity. Nutrients. 2018; 10(5): 605, CrossRef.
Heymsfield SB, Gonzalez MCC, Shen W, Redman L, Thomas D. Weight loss composition is one-fourth fat-free mass: A critical review and critique of this widely cited rule. Obes Rev; 15(4): 310-21, CrossRef.
Wang M, Tan Y, Shi Y, Wang X, Liao Z, Wei P. Diabetes and sarcopenic obesity: Pathogenesis, diagnosis, and treatments. Front Endocrinol. 2020; 11: 568, CrossRef.
Cheah KJ, Cheah LJ. Benefits and side effects of protein supplementation and exercise in sarcopenic obesity: A scoping review. Nutr J. 2023; 22(1): 52, CrossRef.
Meiliana A, Dewi NM, Wijaya A. Nutritional influences on epigenetics, aging and disease. Indones Biomed J. 2019; 11(1): 16-29, CrossRef.
Backx EMP, Tieland M, Borgonjen-Van Den Berg KJ, Claessen PR, Van Loon LJC, De Groot LCPGM. Protein intake and lean body mass preservation during energy intake restriction in overweight older adults. Int J Obes. 2016; 40(2): 299-304, CrossRef.
Petroni ML, Caletti MT, Grave RD, Bazzocchi A, Aparisi Gómez MP, Marchesini G. Prevention and treatment of sarcopenic obesity in women. Nutrients. 2019; 11(6): 1302, CrossRef.
Nicklas BJ, Chmelo E, Delbono O, Carr JJ, Lyles MF, Marsh AP. Effects of resistance training with and without caloric restriction on physical function and mobility in overweight and obese older adults: a randomized controlled trial. Am J Clin Nutr. 2015; 101(5): 991-9, CrossRef.
Bellia A, Garcovich C, D'Adamo M, Lombardo M, Tesauro M, Donadel G, et al. Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects. Intern Emerg Med. 2013; 8(1): 33-40, CrossRef.
Hassan-Smith ZK, Jenkinson C, Smith DJ, Hernandez I, Stuart AM, Crabtree NJ, et al. 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 exert distinct effects on human skeletal muscle function and gene expression. PLoS One. 2017; 12(2): e0170665, CrossRef.
Moyer VA. Vitamin D and calcium supplementation to prevent fractures in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013; 158(9): 691-6, CrossRef.
Sohl E, De Jongh RT, Heijboer AC, Swart KMA, Brouwer-Brolsma EM, Enneman AW, et al. Vitamin D status is associated with physical performance: The results of three independent cohorts. Osteoporos Int. 2013; 24(1): 187-96, CrossRef.
Jung UJ. Sarcopenic obesity: Involvement of oxidative stress and beneficial role of antioxidant flavonoids. Antioxidants. 2023; 12(5): 1063, CrossRef.
Kim JS, Wilson JM, Lee SR. Dietary implications on mechanisms of sarcopenia: roles of protein, amino acids and antioxidants. J Nutr Biochem. 2010; 21(1): 1-13, CrossRef.
Kim J, Lee Y, Kye S, Chung YS, Kim KM. Association of vegetables and fruits consumption with sarcopenia in older adults: The Fourth Korea National Health and Nutrition Examination Survey. Age Ageing. 2015; 44(1): 96-102, CrossRef.
Hutchins-Wiese HL, Kleppinger A, Annis K, Liva E, Lammi-Keefe CJ, Durham HA, et al. The impact of supplemental N-3 long chain polyunsaturated fatty acids and dietary antioxidants on physical performance in postmenopausal women. J Nutr Health Aging. 2013; 17(1): 76-80, CrossRef.
Cesari M, Demougeot L, Boccalon H, Guyonnet S, Vellas B, Andrieu S. The multidomain intervention to prevent disability in elders (MINDED) project: Rationale and study design of a pilot study. Contemp Clin Trials. 2014; 38(1): 145-54, CrossRef.
Tikkanen P, Lönnroos E, Sipilä S, Nykänen I, Sulkava R, Hartikainen S. Effects of comprehensive geriatric assessment-based individually targeted interventions on mobility of pre-frail and frail community-dwelling older people. Geriatr Gerontol Int. 2015; 15(1): 80-8, CrossRef.
DOI: https://doi.org/10.18585/inabj.v16i4.3176
Copyright (c) 2024 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
