Obesity as a predictor of metabolic deviations and the purpose for the personified impact
Abstract
This review is devoted to a description of the factors that underlie various phenotypes of obesity, their interrelationships, a predictor role in predicting metabolic health, maintaining it, in response to various options for therapeutic interventions.The review covered only key parameters: the role of the localization and morphology of adipose tissue in its metabolic activity and secretome characteristics, the role of the main adipokines and hormones involved in the regulation of nutritional metabolism, regulation of appetite and eating behavior and sensitivity to them in the development of obesity of various phenotypes.The role of unmodifiable factors (age and gender) is outlined, and the prospects for using these data in the fight against the obesity epidemic are briefly described.
About the Authors
A. Yu. Babenko
World-Class Research Centre for Personalized Medicine
Russian Federation
Russian Federation
Babenko Alina Yu., MD, Dr. Sc., Head of the Research Institute of Genetic Risks and Personalized Personal Prevention
Akkuratova str. 2, Saint Petersburg, Russia, 197341
T. I. Golikova
World-Class Research Centre for Personalized Medicine
Russian Federation
Russian Federation
Golikova Tatyana Igorevna, Junior Researcher, Research Laboratory of Prediabetes and Other Metabolic Disorders, Research Institute of Genetic Risks and Personalized Prevention
Saint Petersburg
References
1. Keith SW, Redden DT, Katzmarzyk PT, et al. Putative contributors to the secular increase in obesity: exploring the roads less traveled. Int J Obes (Lond). 2006;30(11):1585–1594. DOI: 10.1038/sj.ijo.0803326.
2. Morigny P, Bouche J, Arner P, et al. Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics. Nat Rev Endocrinol. 2021;17(5):276–295. DOI: 10.1038/s41574-021-00471-8.
3. Chen GC, Arthur R, Iyengar NM, et al. Association between regional body fat and cardiovascular disease risk among postmenopausal women with normal body mass index. Eur Heart J. 2019;40(34):2849–2855. DOI: 10.1093/eurheartj/ehz391.
4. Laforest S, Labrecque J, Michaud A, et al. Adipocyte size as a determinant of metabolic disease and adipose tissue dysfunction. Crit Rev Clin Lab Sci. 2015;52(6):301–313. DOI: 10.3109/10408363.2015.1041582.
5. Tandon P, Wafer R, Minchin JEN. Adipose morphology and metabolic disease. J Exp Biol. 2018;221(Pt Suppl 1):jeb164970. DOI: 10.1242/jeb.164970.
6. Hoffstedt J, Arner E, Wahrenberg H, et al. Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity. Diabetologia. 2010;53(12):2496–2503. DOI: 10.1007/s00125-010-1889-3.
7. Veilleux A, Caron-Jobin M, Noel S, et al. Visceral adipocyte hypertrophy is associated with dyslipidemia independent of body composition and fat distribution in women. Diabetes. 2011;60(5):1504–1511. DOI: 10.2337/db10-1039.
8. Lonn M, Mehlig K, Bengtsson C, et al. Adipocyte size predicts incidence of type 2 diabetes in women. FASEB J. 2010;24(1):326–331. DOI: 10.1096/fj.09-133058.
9. Stenkula KG, Erlanson-Albertsson C. Adipose cell size: importance in health and disease. Am J Physiol Regul Integr Comp Physiol. 2018;315(2):284–295. DOI: 10.1152/ajpregu.00257.2017.
10. Jung CH, Lee WJ, Song KH. Metabolically healthy obesity: a friend or foe? Korean J Intern Med. 2017;32(4): 611–621. DOI: 10.3904/kjim.2016.259.
11. Rey-López JP, de Rezende LF, Pastor-Valero M, et al. The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used. Obes Rev. 2014;15(10):781–790. DOI: 10.1111/obr.12198
12. Bo S, Musso G, Gambino R, et al. Prognostic implications for insulin-sensitive and insulin-resistant normal-weight and obese individuals from a populationbased cohort. Am J Clin Nutr. 2012;96(5):962–969. DOI: 10.3945/ajcn.112.040006.
13. Kloting N, Fasshauer M, Dietrich A, et al. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010;299(3):E506–515. doi: 10.1152/ajpendo.00586.2009.
14. Tang A, Coster ACF, Tonks KT, et al. Longitudinal changes in insulin resistance in normal weight, overweight and obese individuals. J Clin Med. 2019;8(5):623. DOI: 10.3390/jcm8050623.
15. Packer M. Differential pathophysiological mechanisms in heart failure with a reduced or preserved ejection fraction in diabetes. JACC Heart Fail. 2021;9(8):535–549. DOI: 10.1016/j.jchf.2021.05.019.
16. Roos V, Elmståhl S, Ingelsson E, et al. Metabolic syndrome development during aging with special reference to obesity without the metabolic syndrome. Metab Syndr Relat Disord. 2017;15(1):36–43. DOI: 10.1089/met.2016.0082.
17. Zheng R, Liu C, Wang C, et al. Natural course of metabolically healthy overweight/obese subjects and the impact of weight change. Nutrients. 2016;8(7):430. DOI: 10.3390/nu8070430.
18. Khan UI, Wang D, Karvonen-Gutierrez CA, et al. Progression from metabolically benign to at-risk obesity in perimenopausal women: a longitudinal analysis of Study of Women Across the Nation (SWAN). J Clin Endocrinol Metab. 2014;99(7):2516–2525. DOI: 10.1210/jc.2013-3259.
19. Kabat GC, Wu WY-Y, Bea JW, et al. Metabolic phenotypes of obesity: frequency, correlates and change over time in a cohort of postmenopausal women. Int J Obes (Lond). 2017;41(1):170–177. DOI: 10.1038/ijo.2016.179.
20. Hwang Y-C, Hayashi T, Fujimoto WY, et al. Visceral abdominal fat accumulation predicts the conversion of metabolically healthy obese subjects to an unhealthy phenotype. Int J Obes. 2015;39(9):1365–1370. DOI: 10.1038/ijo.2015.75.
21. Bell JA, Hamer M, Sabia S, et al. The natural course of healthy obesity over 20 years. J Am Coll Cardiol. 2015;65(1):101–102. DOI: 10.1016/j.jacc.2014.09.077.
22. Appleton SL, Seaborn CJ, Visvanathan R, et al. Diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: a cohort study. Diabetes Care. 2013;36(8):2388–2394. DOI: 10.2337/dc12-1971.
23. Zembic А, Eckel N, Stefan N, et al. An empirically derived definition of metabolically healthy obesity based on risk of cardiovascular and total mortality. JAMA Netw Open. 2021;4(5):e218505. DOI: 10.1001/
24. jamanetworkopen.2021.8505.
25. Stefan N. Causes, consequences, and treatment of metabolically unhealthy fat distribution. Lancet Diabetes Endocrinol. 2020;8(7):616–627. DOI: 10.1016/S2213-8587(20)30110-8.
26. Lotta LA, Wittemans LBL, Zuber V, et al. Association of genetic variants related to gluteofemoral vs abdominal fat distribution with type 2 diabetes, coronary disease, and cardiovascular risk factors. JAMA. 2018;320(24):2553–2563. DOI: 10.1001/jama.2018.19329.
27. Neeland IJ, Poirier P, Despres JP. Cardiovascular and metabolic heterogeneity of obesity: clinical challenges and implications for management. Circulation. 2018;137(13):1391–1406. DOI: 10.1161/CIRCULATIONAHA.117.029617
28. Pischon T, Boeing H, Hoffmann K, et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med. 2008;359(20):2105–2120. DOI: 10.1056/NEJMoa0801891
29. Haring HU. Novel phenotypes of prediabetes? Diabetologia. 2016;599):1806–1818. DOI: 10.1007/s00125-016-4015-3.
30. Lee MJ, Kim E-H, Bae SJ, et al. Protective role of skeletal muscle mass against progression from metabolically healthy to unhealthy phenotype. Clin Endocrinol (Oxf). 2019;90(1):102–113. DOI: 10.1111/cen.13874.
31. Lidell ME, Betz MJ, Dahlqvist LO, et al. Evidence for two types of brown adipose tissue in humans. Nat Med. 2013;19(5):631–634. DOI: 10.1038/nm.3017.
32. Matsushita M, Yoneshiro T, Aita S, et al. Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. Int J Obes (Lond) 2014;38(6):812–817. DOI: 10.1038/ijo.2013.206.
33. Orava J, Nuutila P, Noponen T, et al. Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans. Obesity (Silver Spring). 2013;21(11):2279–2287. DOI: 10.1002/oby.20456.
34. Raiko J, Holstila M, Virtanen KA, et al. Brown adipose tissue triglyceride content is associated with decreased insulin sensitivity independent of age and obesity. Diabetes Obes Metab. 2015;17(5):516–519. DOI: 10.1111/dom.12433.
35. Cleasby ME, Jamieson PM, Atherton PJ. Insulin resistance and sarcopenia: mechanistic links between common co-morbidities. J Endocrinol. 2016;229(2):R67–R81. DOI: 10.1530/JOE-15-0533.
36. Gerst F, Wagner R, Oquendo MB, еt al. What role do fat cells play in pancreatic tissue? Mol Metab. 2019;25:1–10. DOI: 10.1016/j.molmet.2019.05.001.
37. Stout MB, Tchkonia T, Kirkland JL. The aging adipose organ: lipid redistribution, inflammation, and cellular senescence. In: Adipose Tissue and Adipokines in Health and Disease, edited by Fantuzzi G, Braunschweig C. New York: Humana.2014;69–80.
38. Mourkioti F, Kratsios P, Luedde T, et al. Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration. J Clin Invest. 2006;116(11): 2945–2954. DOI: 10.1172/JCI28721.
39. Karagiannides I, Tchkonia T, Dobson DE, et al. Altered expression of C/EBP family members results in decreased adipogenesis with aging. Am J Physiol Regul Integr Comp Physiol. 2001;280(6):R1772–1780. DOI: 10.1152/ajpregu.2001.280.6.R1772.
40. Schipper BM, Marra KG, Zhang W, et al. Regional anatomic and age effects on cell function of human adipose-derived stem cells. Ann Plastic Surg.2008;60(5):538–544. DOI: 10.1097/SAP.0b013e3181723bbe.
41. Stout MB, Justice JN, Nicklas BJ, et al. Physiological aging: links among adipose tissue dysfunction, diabetes, and frailty. Physiology (Bethesda). 2017;32(1):9–19. DOI: 10.1152/physiol.00012.2016.
42. Mack I, BelAiba RS, Djordjevic T, et al. Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNFalpha exposure. Am J Physiol Endocrinol Metab. 2009;297(3):735–748. DOI: 10.1152/ajpendo.90851.2008.
43. Tchkonia T, Morbeck DE, Von Zglinicki T, et al. Fat tissue, aging, and cellular senescence. Aging Cell. 2010;9(5):667–684. DOI: 10.1111/j.1474-9726.2010.00608.x.
44. Zhu Y, Tchkonia T, Stout MB, et al. Inflammation and the depot-specific secretome of human preadipocytes. Obesity (Silver Spring).2015;23(5):989–999. DOI: 10.1002/oby.21053.
45. Lumeng CN, Liu J, Geletka L, et al. Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. J Immunol. 2011;187(12):6208–6216. DOI: 10.4049/jimmunol.1102188.
46. Xu M, Palmer AK, Ding H, et al. Targeting senescent cells enhances adipogenesis and metabolic function in old age. 2015;4:e12997. DOI: 10.7554/eLife.12997.
47. Lee PG, Halter JB. The pathophysiology of hyperglycemia in older adults: clinical considerations. Diabetes Care. 2017;40(4): 444–452. DOI: 10.2337/dc16-1732.
48. Babenko AY, Matveev GA, Alekseenko TI, et al. Interrelations of components of metabolic syndrome with the level of the hormones involved in regulation of adipose tissue metabolism. Arterial Hypertension. 2019;25(6):639–652. DOI: 10.18705/1607-419X-2019-25-6-639-652.
49. Singh R, Artaza JN, Taylor WE, et al. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003;144(11):5081–5088. DOI: 10.1210/en.2003-0741.
50. Buvat J, Maggi M, Guay A, et al. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med. 2013;10(1):245–284. DOI: 10.1111/j.1743-6109.2012.02783.x.
51. Childs GV, Odle AK, MacNicol MC, et al. The importance of leptin to reproduction. Endocrinology. 2021;162(2):bqaa204. DOI: 10.1210/endocr/bqaa204.
52. Gavin KM, Cooper EE, Raymer DK, et al. Estradiol effects on subcutaneous adipose tissue lipolysis in premenopausal women are adipose tissue depot specific and treatment dependent. Am J Physiol Endocrinol Metab. 2013;304(11):1167–1174. DOI: 10.1152/ajpendo.00023.2013.
53. Clegg DJ, Brown LM, Woods SC, et al. Gonadal hormones determine sensitivity to central leptin and insulin. Diabetes. 2006;55(4):978–987. DOI: 10.2337/diabetes.55.04.06.db05-1339.
54. Musatov S, Chen W, Pfaff DW, et al. Silencing of estrogen receptor alpha in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. Proc Natl Acad Sci USA. 2007;104(7):2501–2506. DOI: 10.1073/pnas.0610787104.
55. Petersen EW, Carey AL, Sacchetti M, et al. Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro. Am J Physiol Endocrinol Metab. 2005;288(1):E155–E162. DOI: 10.1152/ajpendo.00257.2004.
56. Nookaew I, Svensson P-A, Jacobson P, et al. Adipose tissue resting energy expenditure and expression of genes involved in mitochondrial function are higher in women than in men. J Clin Endocrinol Metab. 2013;98(2):E370–E378. DOI: 10.1210/jc.2012-2764.
57. Kolb H, Kempf K, Röhling M, et al. Insulin: too much of a good thing is bad. BMC Medicine. 2020;18(1):224. DOI: 10.1186/s12916-020-01688-6.
58. Schnurbein J, Manzoor J, Brandt S, et al. Leptin is not essential for obesity-associated hypertension. Obes Facts. 2019;12(4):460–475. DOI: 10.1159/000501319.
59. Pereira S, Cline DL, Glavas MM, et al. Tissuespecific effects of leptin on glucose and lipid metabolism. Endocr Rev. 2021;42(1):1–28. DOI: 10.1210/endrev/bnaa027.
60. Mittendorfer B, Horowitz JF, DePaoli AM, et al. Recombinant human leptin treatment does not improve insulin action in obese subjects with type 2 diabetes. Diabetes. 2001;60(5):1474–1477. DOI: 10.2337/db10-1302.
61. Caro JF, Kolaczynski JW, Nyce MR, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet. 1996;348(9021):159–161. DOI: 10.1016/s0140-6736(96)03173-x.
62. Sinha MK, Ohannesian JP, Heiman ML, et al. Nocturnal rise of leptin in lean, obese, and noninsulin- dependent diabetes mellitus subjects. J Clin Invest. 1996;97(5):1344–1347. DOI: 10.1172/JCI118551.
63. Barr VA, Malide D, Zarnowski MJ, et al. Insulin stimulates both leptin secretion and production by rat white adipose tissue. Endocrinology. 1997;138(10):4463–4472. DOI: 10.1210/endo.138.10.5451.
64. Saladin R, De Vos P, Guerre-Millo M, et al. Transient increase in obese gene expression after food intake or insulin administration. Nature. 1995;377(6549):527–529. DOI: 10.1038/377527a0.
65. Dodd GT, Descherf S, Loh K, et al. Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell. 2015;160(1-2):88–104. DOI: 10.1016/j.cell.2014.12.022.
66. Sobhani I, Bado A, Vissuzaine C, et al. Leptin secretion and leptin receptor in the human stomach. 2000;47(2):178–183. DOI: 10.1136/gut.47.2.178.
67. Sobhani I, Buyse M, Goiot H, et al. Vagal stimulation rapidly increases leptin secretion in human stomach. Gastroenterology. 2002;122(2):259–263. DOI: 10.1053/gast.2002.31385.
68. Martin RL, Perez E, He YJ, et al. Leptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation. Metabolism. 2000;49(11):1479–1484. DOI: 10.1053/meta.2000.17695.
69. Zhang Y, Olbort M, Schwarzer K, et al. The leptin receptor mediates apparent autocrine regulation of leptin gene expression. Biochem Biophys Res Commun.1997;240(2):492–495. DOI: 10.1006/bbrc.1997.7622.
70. Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79–83. DOI: 10.1006/bbrc.1999.0255.
71. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005;96(9):939–949. DOI: 10.1161/01.RES.0000163635.62927.34.
72. Fasshauer M, Kralisch S, Klier M, et al. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2003;301(4):1045–1050. DOI: 10.1016/0006-291x(03)00090-1.
73. Engeli S, Feldpausch M, Gorzelniak K, et al. Association between adiponectin and mediators of inflammation in obese women. Diabetes. 2003;52(4):942–947. DOI: 10.1507/endocrj.K07-032.
74. Hattori Y, Akimoto K, Gross SS, et al. Angiotensin- II-induced oxidative stress elicits hypoadiponectinaemia in rats. Diabetologia. 2005;48(6):1066–1074. DOI: 10.1007/s00125-005-1766-7.
75. Hosogai N, Fukuhara A, Oshima K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes. 2007;56(4):901–911. DOI: 10.2337/db06-0911.
76. Maeda N, Shimomura I, Kishida K, et al. Dietinduced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8(7):731–737. DOI: 10.1038/nm724.
77. Kim J-Y, Van De Wall E, Laplante M, et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007;117(9):2621–2637. DOI: 10.1172/JCI31021.
78. Vasileva LB, Artemyeva MS, Ma Y, et al. The effect of obesity, impaired carbohydrate metabolism and bariatric surgery on adiponectin and leptin mRNA levels in different adipose tissue depots. Arterial Hypertension. 2019;25(5):568–576. DOI: 10.18705/1607-419X-2019-25-5-568-576.
79. Anandhakrishnan А, Korbonits М. Glucagon-like peptide-1 in the pathophysiology and pharmacotherapy of clinical obesity. World J Diabetes. 2016;7(20):572–598. DOI: 10.4239/wjd.v7.i20.572.
80. Yamaoka-Tojo M, Tojo T, Takahira N, et al. Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease. Cardiovasc Diabetol. 2010;9:17. DOI: 10.1186/1475-2840-9-17.
81. Cho YM, Fujita Y, Kieffer TJ. Glucagon-like peptide-1: glucose homeostasis and beyond. Annu Rev Physiol. 2014;76:535–559. DOI: 10.1146/annurevphysiol-021113-170315.
82. Møller CL, Vistisen D, Færch K, et al. Glucose- Dependent Insulinotropic Polypeptide Is Associated With Lower Low-Density Lipoprotein But Unhealthy Fat Distribution, Independent of Insulin: The ADDITIONPRO Study. J Clin Endocrinol Metab. 2016;101(2):485–493. DOI: 10.1210/jc.2015-3133.
83. Gasbjerg LS, Gabe MBN, Hartmann B, et al. Glucose-dependent insulinotropic polypeptide (GIP) receptor antagonists as anti-diabetic agents. Peptides. 2018;100:173–181. DOI: 10.1016/j.peptides.2017.11.021.
84. Ariyasu H, Takaya K, Tagami T, et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab. 2001;86(10):4753–47538. DOI: 10.1210/jcem.86.10.7885.
85. Korbonits M, Bustin SA, Kojima M, et al. The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J Clin Endocrinol Metab. 2001;86(2):881–887. DOI: 10.1210/jcem.86.2.7190.
86. Date Y, Nakazato M, Hashiguchi S, et al. Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin secretion. Diabetes. 2002;51(1):124–129. DOI: 10.2337/diabetes.51.1.124.
87. Volante M, Allia E, Gugliotta P, et al. Expression of ghrelin and of the GH secretagogue receptor by pancreatic islet cells and related endocrine tumors. J Clin Endocrinol Metab. 2002;87(3):1300–1308. DOI: 10.1210/jcem.87.3.8279.
88. Wierup N, Svensson H, Mulder H, et al. The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas. Regul Pept. 2002;107(1-3):63–69. DOI: 10.1016/s0167-0115(02)00067-8.
89. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–660. DOI: 10.1038/45230.
90. Inui A, Asakawa A, Bowers CY, et al. Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J. 2004;18(3):439–456. DOI: 10.1096/fj.03-0641rev.
91. Mori K, Yoshimoto A, Takaya K, et al. Kidney produces a novel acylated peptide, ghrelin. FEBS Lett. 2000;486(3):213–216. DOI: 10.1016/s0014-5793(00)02308-5.
92. Tena-Sempere M, Barreiro ML, Gonzalez LC, et al. Novel expression and functional role of ghrelin in rat testis. Endocrinology. 2002;143(2):717–725. DOI: 10.1210/endo.143.2.8646.
93. Gualillo O, Caminos J, Blanco M, et al. Ghrelin, a novel placental-derived hormone. Endocrinology. 2001;142(2):788–794. DOI: 10.1210/endo.142.2.7987.
94. Hattori N, Saito T, Yagyu T, et al. GH, GH receptor, GH secretagogue receptor,and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab. 2001;86(9):4284–4291. DOI: 10.1210/jcem.86.9.7866.
95. Pinkney J, Williams G. Ghrelin gets hungry. Lancet. 2002;359(9315):1360–1361. DOI: 10.1016/S0140-6736(02)08387-3.
96. Lee H-M, Wang G, Englander EW, et al. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology. 2002;143(1):185–190. DOI: 10.1210/endo.143.1.8602.
97. Toshinai K, Mondal MS, Nakazato M, et al. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem Biophys Res Commun. 2001;281(5):1220–1225. DOI: 10.1006/bbrc.2001.4518.
98. Lindqvist A, Erlanson-Albertsson C. Fat Digestion and its Role in Appetite Regulation and Energy Balance -The Importance of Enterostatin and Tetrahydrolipstatin. Curr Med Chem — Central Nervous System Agents. 2003;3:157–175. DOI: 10.2174/1568015033477712.
99. Inui A. Ghrelin: an orexigenic and somatotrophic signal from stomach. Nat Rev Neurosci. 2001;2(8):551–560. DOI: 10.1038/35086018.
100. Tschop M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50(4):707–709. DOI: 10.2337/diabetes.50.4.707.
101. Hansen TK, Dall R, Hosoda H, et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol (Oxf). 2002;56(2):203–206. DOI: 10.1046/j.0300-0664.2001.01456.x.
102. English PJ, Ghatei MA, Malik IA, et al. Food fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab. 2002:87(6):2984–2987. DOI: 10.1210/jcem.87.6.8738.
103. Ligthart S, Hasbani NR, Ahmadizar F, et al. Genetic susceptibility, obesity and lifetime risk of type 2 diabetes: The ARIC study and Rotterdam Study. Diabet Med. 2021;38(10):e14639. DOI: 10.1111/dme.14639.
104. Mahajan A, Taliun D, Thurner M, et al. Finemapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet. 2018;50(11):1505–1513. DOI: 10.1038/s41588-018-0241-6.
105. Tinahones FJ, Coín-Aragüez L, Mayas MD, et al. Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels. BMC Physiol. 2012;12:4. DOI: 10.1186/1472-6793-12-4.
106. Tsiotra PC, Boutati E, Dimitriadis G, et al. High insulin and leptin increase resistin and inflammatory cytokine production from human mononuclear cells. Biomed Res Int. 2013;2013:487081. DOI: 10.1155/2013/487081.
107. Pereira-Fernandes A, Dirinck E, Dirtu AC, et al. Expression of obesity markers and Persistent Organic Pollutants levels in adipose tissue of obese patients: reinforcing the obesogen hypothesis? PLoS One. 2014;9(1):e84816. DOI: 10.1371/journal.pone.0084816.
108. Cano-Martínez LJ, Marroquín C, Coral-Vázquez RM, et al. Expression of adipokines and their receptors in adipose tissue of women with class 3 obesity with or without hypertension. Gene. 2019;702:148–152. DOI: 10.1016/j.gene.2019.03.070.
109. Konigorski S, Janke J, Drogan D, et al. Prediction of circulating adipokine levels based on body fat compartments and adipose tissue gene expression. Obes Facts. 2019;12(6):590–605. DOI: 10.1159/000502117.
110. Morselli E, Fuente-Martin E, Finan B, et al. Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα. Cell Rep. 2014;9(2):633–645. DOI: 10.1016/j.celrep.2014.09.025.
111. Taylor R. Calorie restriction for long-term remission of type 2 diabetes. Clin Med (Lond). 2019;19(1):37–42. DOI: 10.7861/clinmedicine.19-1-37.
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Babenko A.Yu., Golikova T.I. Obesity as a predictor of metabolic deviations and the purpose for the personified impact. Russian Journal for Personalized Medicine. 2021;1(1):59-94.
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