Know your Enemy: Nature and Biochemistry of Obesity
Abstract
Obesity represents a serious medical condition and has nowadays reached pandemic proportions. Comorbidities associated with obesity are severe, and affect almost all organ systems. Adipose tissue has several important functions: to provide energy storage, maintain body temperature through the process of thermogenesis, and maintain balance in a variety of metabolic patterns. Adipose tissue is an endocrine organ with numerous biochemical roles, and in obese individuals adipose tissue becomes either hypertrophic or hyperplastic, with impaired function. The immune system activity and metabolic regulation in adipose tissue are extremely related processes. A loss of balance on this axis causes numerous disorders associated with obesity, and the basis of these disorders is insulin resistance, which is a hallmark of obesity. Hormones that are almost exclusively produced in adipocytes and studied in various biochemistry processes are leptin, adiponectin and resistin. Successful treatment of obesity nowadays involves lifestyle and diet modification, pharmacotherapy, mainly with glucagon-like peptide-1 agonists, and bariatric surgery, which remains the most effective treatment method for the selected population of severely obese individuals. Positive effects of bariatric surgery are reflected not only in a restriction of food intake, but in hormonal changes, especially those of gut hormones responsible for hunger regulation and energy metabolism.
References
Fan H, Zhang X. Recent trends in overweight and obesity in adolescents aged 12 to 15 years across 21 countries. Pediatr Obes. 2021;17(1):e12839.
Wang K, Wu C, Yao Y, Zhang S, Xie Y, Shi K, et al. Association between socio-economic factors and the risk of overweight and obesity among Chinese adults: A retrospective cross-sectional study from the China Health and Nutrition Survey. Glob Health Res Policy. 2022;7(1):41.
Evans A, Tolonen H, Hense H, Ferrario M, Sans S, Kuulasmaa K. Trends in coronary risk factors in the WHO MONICA project. Int J Epidemiol. 2001;30(1):35-40.
Ruiz-Hurtado G, Ruilope LM. Hypertension and obesity: correlate with renin-angiotensin-aldosterone system and uric acid. J Clin Hypertens (Greenwich). 2014;16(8):559-60.
Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease. J Am Coll Cardiol. 2009;53(21):1925-32.
Yamada T, Kimura-Koyanagi M, Sakaguchi K, Ogawa W, Tamori Y. Obesity and risk for its comorbidities diabetes, hypertension, and dyslipidemia in Japanese individuals aged 65 years. Sci Rep. 2023;13(1):2346.
Tadese K, Ernst V, Weaver AL, Thacher TD, Rajjo T, Kumar S, et al. Association of perinatal factors with severe obesity and dyslipidemia in adulthood. J Prim Care Community Health. 2022;13:21501327211058982.
Nova S, Irawan R, Widjaja NA, Irwanto I. Vcam-1 values in obese adolescents with dyslipidemia and insulin resistance. Int J Sci Adv. 2022;3(1):105-10.
Talbot CV, Branley-Bell D. #BetterHealth: A qualitative analysis of reactions to the UK government's better health campaign. J Health Psychol. 2022;27(5):1252-8.
Dewa LH, Lavelle M, Pickles K, Kalorkoti C, Jaques J, Pappa S, et al. Young adults' perceptions of using wearables, social media and other technologies to detect worsening mental health: A qualitative study. PLoS One. 2019;14(9):e0222655.
World Health Organization [Internet]. Obesity and overweight [cited 2024 May 27]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
Sikaris KA. The Clinical Biochemistry of Obesity. Clin Biochem Rev. 2004;25:165-81.
Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277-359.
Carobbio S, Pellegrinelli V, Vidal-Puig A. Adipose tissue function and expandability as determinants of lipotoxicity and the metabolic syndrome. Adv Exp Med Biol. 2017;960:161-96.
Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Metab. 2010;298(6):1244-53.
Cinti S. Pink adipocytes. Trends Endocrinol Metab. 2018;29(9):651-66.
Giordano A, Smorlesi A, Frontini A, Barbatelli G, Cinti S. Mechanisms in Endocrinology: White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ. Eur J Endocrinol. 2014;170(5):159-71.
Saponaro C, Gaggini M, Carli F, Gastaldelli A. The Subtle balance between lipolysis and lipogenesis: A Critical Point in Metabolic Homeostasis. Nutrients. 2015;7:9453-74.
Braun K, Oeckl J, Westermeier J, Li Y, Klingenspor M. Non-adrenergic control of lipolysis and thermogenesis in adipose tissues. J Exp Biol. 2018;221:1-14.
Fielding BA, Frayn KN. Lipoprotein lipase and the disposition of dietary fatty acids. Br J Nutr. 1998;80(6):495–502.
Richard AJ, White U, Elks CM, Stephens JM, Feingold KR, Anawalt B, et al. Adipose Tissue: physiology to metabolic dysfunction. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000- [updated 2020 Apr 4; cited 2024 May 27]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555602/
Gorin E, Tal-Or Z, Shafrir E. Glyceroneogenesis in adipose tissue of fasted, diabetic and triamcinolone treated rats. Eur J Biochem. 1969;8(3):370-5.
Ishibashi K, Fujioka T, Ui M. Insulin increased cAMP phosphodiesterase activity antagonizing metabolic actions of glucagon in rat hepatocytes cultured with herbimycin A. Eur J Pharmacol. 2000;409(2):109-21.
Smedley I, Lubrzynska E. The biochemical synthesis of the fatty acids. Biochem J. 1913;7:364-74.
Koundouros N. Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122:4-22.
Batchuluun B, Pinkosky SL, Steinberg GR. Lipogenesis inhibitors: therapeutic opportunities and challenges. Nat Rev Drug Discov. 2022;21:283-305.
Luo L, Liu M. Adipose tissue in control of metabolism. J Endocrinol. 2016;231(3):77-99.
Hansen JS, de Mare S, Jones HA, Goransson O, Lindkvist- Petersson K. Visualization of lipid directed dynamics of perilipin1 in human primary adipocytes. Sci Rep. 2017;7:15011.
Bombarda-Rocha V, Silva D, Badr-Eddine A, Nogueira P, Gonçalves J, Fresco P. Challenges in pharmacological intervention in perilipins (PLINs) to modulate lipid droplet dynamics in obesity and cancer. Cancers. 2023;15:4013.
Westhoff CC, Mrozinski J, Riedel I, Heid HW, Moll R. Perilipin 1 is a highly specific marker for adipocytic differentiation in sarcomas with intermediate sensitivity. J Cancer Res Clin Oncol. 2017;143:225-32.
Ota T. Obesity- induced inflammation and insulin resistance. Front Endocrinol. 2014;5:204.
Chawla A, Nguzen KD, Goh YP. Macrophage- induced inflammation in metabolic diseases. Nat Rev Immunol. 2011;11:738-49.
Bakarat B, Almeida MEF. Biochemical and immunological changes in obesity. Arch Biochem Biophys. 2021;708:108951.
Meyts PD, Sajid W, Palsgaard J, Theede AM, Gauguin L, Aladdin H, et al. Insulin and IGF-1 Receptor Structure and Binding Mechanism. In: Saltiel AR, Pessin JE, editors. Mechanisms of Insulin Action. New York, NY: Springer; 2007; p. 1-32.
Scheja L, Heeren J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat Rev Endocrinol. 2019;15(9):507-24.
Asghar A, Sheikh N. Role of immune cells in obesity induced low grade inflammation and insulin resistance. Cell Immunol. 2017;315:18-26.
Dhatariya KK. Defining and characterizing diabetic ketoacidosis in adults. Diabetes Res Clin. 2019;155:107797.
Savage MW, Dhatariya KK, Kilvert A, Rayman G, Rees JA, Courtney CH, et al. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diab Med. 2011;28(5):508-15.
Agiostratidou G, Anhalt H, Ball D, Blonde L, Gourgari E, Harriman KN, et al. Standardizing clinically meaningful outcome measures beyond HbA1c for type 1 diabetes: a consensus report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange. Diab Care. 2017;40(12):1622-30.
Yang Q, Vijayakumar A, Kahn BB. Metabolites as regulators of insulin sensitivity and metabolism. Nat Rev Mol Cell Biol. 2018;19:654-72.
Costa JV, Duarte JS. Adipose tissue and adipokines. Acta Med Port. 2006;19:251-6.
Saetang J, Sangkhathat S. Role of innate lymphoid cells in obesity and metabolic disease. Mol Med Rep. 2018;17(1):1403-12.
Matsuzawa Y. The metabolic syndrome and adipocytokines. FEBS Lett. 2006;580:2917-21.
Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013;2:192-200.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425-32.
Gruzdeva O, Borodkina D, Uchasova E, Dyleva Y, Barbarash O. Leptin resistance: underlying mechanisms and diagnosis. Diabetes Metab Syndr Obes. 2019;12:191-8.
Cowley MA, Smart JL, Rubinstein M, Cerdar MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature. 2001;411:480-4.
Heijboer AC, van den Hoek AM, Pijl H, Voshol PJ, Havekes LM, Romijn JA, et al. Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice. Diabetologia. 2005;48:1621-6.
Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep. 2001;2:282-6.
Combs TP, Marliss EB. Adiponectin signaling in the liver. Rev Endocr Metab Disord. 2014;15(2):137-47.
Combs TP, Berg AH, Obici S, Scherer PE, Rossetti L. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest. 2001;108(12):1875-81.
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.
Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature. 2013;503(7477):493-9.
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307-12.
Patel SD, Rajala MW, Rossetti L, Scherer PE, Shapiro L. Disulfide-dependent multimeric assembly of resistin family hormones. Science. 2004;304:1154-8.
Lee S, Lee HC, Kwon YW, Lee SE, Cho Y, Kim J, et al. Adenylyl cyclase-associated protein 1 is a receptor for human resistin and mediates inflammatory actions of human monocytes. Cell Metab. 2014;19(3):484-97.
Johnson V R, Bowen-Jallow KA, Stanford FC. A call to action: multi-disciplinary care and treatment of obesity in pediatrics. Pediatr Investig. 2021;5(1):1-2.
Miguel-Etayo PD, Moreno LA, Santabárbara J, Martín-Matillas M, Julian MCA, Marti Del Moral A, et al. Diet quality index as a predictor of treatment efficacy in overweight and obese adolescents: The EVASYON study. Clin Nutr. 2019;38(2):782-90.
Malik IO, Petersen MC, Klein S. Glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon receptor poly-agonists: A new era in obesity pharmacotherapy. Obesity. 2022;30(9):1718-21.
Rogliani P, Matera MG, Calzetta L, Hanania NA, Page C, Rossi I, et al. Long-term observational study on the impact of GLP-1R agonists on lung function in diabetic patients. Respir Med. 2019;154:86-92.
Larraufie P, Roberts GP, McGavigan AK, Kay RG, Li J, Leiter A, et al. Important Role of the GLP-1 Axis for Glucose Homeostasis after Bariatric Surgery. Cell Rep. 2019;26(6):1399-408.
Costa JMMd, Silva PLdS, Rosalem IDS, Pedroni EG, Pessin LP, Pelissari DF, et al. Integrative review of GLP-1 and PYY intestinal hormones in the regulation of appetite and satiety after Roux-en-Y bariatric surgery: Recent evidence in humans. Int J Health Sci. 2023;3(26):2-7.
Lampropoulos C, Mulita F, Alexandrides TK, Kehagias D, Kalavrizioti D, Albanopoulos K, et al. Ghrelin, glucagon-like peptide-1, and peptide YY secretion in patients with and without weight regain during long-term follow-up after bariatric surgery: A cross-sectional study. Prz Menopauzalny. 2022;21(2):97-105.