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From Obesity to Diabetes: The Role of the Adipose Organ

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From Obesity to Diabetes

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 274))

Abstract

Obesity is a complex, multifactorial, and relapsing disease whose prevalence has tripled during the last decades and whose incidence is expected to further increase. For these reasons, obesity is considered as a real pandemic, deeply burdening the global health-care systems. From a pathophysiological standpoint obesity is the result of a chronic-positive energy balance which in turn leads to an excessive accumulation of lipids, not only within the adipose organ, but also in different cytotypes, a phenomenon leading to lipotoxicity that deeply compromises several cellular and organs functions. Obesity is therefore associated with over 200 medical complications, including insulin resistance and type 2 diabetes mellitus (T2DM) and represents the fifth leading cause of death worldwide. In this review, we describe the main pathophysiological mechanisms linking obesity-induced adipose organ dysfunction to insulin resistance and T2DM.

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References

  • Aguirre LE, Colleluori G, Fowler KE, Jan IZ, Villareal K, Qualls C et al (2015) High aromatase activity in hypogonadal men is associated with higher spine bone mineral density, increased truncal fat and reduced lean mass. Eur J Endocrinol 173(2):167–174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • American Diabetes Association (2021) 8. Obesity management for the treatment of type 2 diabetes: standards of medical care in diabetes-2021. Diabetes Care 44(Suppl 1):S100–S110

    Article  Google Scholar 

  • Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM et al (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11(2):191–198

    Article  CAS  PubMed  Google Scholar 

  • Arner E, Westermark PO, Spalding KL, Britton T, Ryden M, Frisen J et al (2010) Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59(1):105–109

    Article  CAS  PubMed  Google Scholar 

  • Barbatelli G, Heinzelmann M, Ferrara P, Morroni M, Cinti S (1994) Quantitative evaluations of gap junctions in old rat brown adipose tissue after cold acclimation: a freeze-fracture and ultra-structural study. Tissue Cell 26(5):667–676

    Article  CAS  PubMed  Google Scholar 

  • Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K et al (2010) The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab 298(6):E1244–E1253

    Article  CAS  PubMed  Google Scholar 

  • Batsis JA, Villareal DT (2018) Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol 14(9):513–537

    Article  PubMed  PubMed Central  Google Scholar 

  • Bel Lassen P, Charlotte F, Liu Y, Bedossa P, Le Naour G, Tordjman J et al (2017) The FAT score, a fibrosis score of adipose tissue: predicting weight-loss outcome after gastric bypass. J Clin Endocrinol Metab 102(7):2443–2453

    Article  PubMed  Google Scholar 

  • Belligoli A, Compagnin C, Sanna M, Favaretto F, Fabris R, Busetto L et al (2019) Characterization of subcutaneous and omental adipose tissue in patients with obesity and with different degrees of glucose impairment. Sci Rep 9(1):11333

    Article  PubMed  PubMed Central  Google Scholar 

  • Bjorntorp P, Rosmond R (1999) Visceral obesity and diabetes. Drugs 58(Suppl 1):13–18; discussion 75–82

    Article  CAS  PubMed  Google Scholar 

  • Blasetti Fantauzzi C, Iacobini C, Menini S, Vitale M, Sorice GP, Mezza T et al (2020) Galectin-3 gene deletion results in defective adipose tissue maturation and impaired insulin sensitivity and glucose homeostasis. Sci Rep 10(1):20070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bluher M (2019) Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol 15(5):288–298

    Article  PubMed  Google Scholar 

  • Bray GA, Kim KK, Wilding JPH, World Obesity Federation (2017) Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev 18(7):715–723

    Article  CAS  PubMed  Google Scholar 

  • Brinkley TE, Hsu FC, Beavers KM, Church TS, Goodpaster BH, Stafford RS et al (2012) Total and abdominal adiposity are associated with inflammation in older adults using a factor analysis approach. J Gerontol A Biol Sci Med Sci 67(10):1099–1106

    Article  PubMed  PubMed Central  Google Scholar 

  • Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C et al (2005) Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54(8):2277–2286

    Article  CAS  PubMed  Google Scholar 

  • Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84(1):277–359

    Article  CAS  PubMed  Google Scholar 

  • Cefalu WT, Rubino F, Cummings DE (2016) Metabolic surgery for type 2 diabetes: changing the landscape of diabetes care. Diabetes Care 39(6):857–860

    Article  PubMed  PubMed Central  Google Scholar 

  • Cerhan JR, Moore SC, Jacobs EJ, Kitahara CM, Rosenberg PS, Adami HO et al (2014) A pooled analysis of waist circumference and mortality in 650,000 adults. Mayo Clin Proc 89(3):335–345

    Article  PubMed  Google Scholar 

  • Cinti S (2012) The adipose organ at a glance. Dis Model Mech 5(5):588–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cinti S (2018a) Adipose organ development and remodeling. Compr Physiol 8(4):1357–1431

    Article  PubMed  Google Scholar 

  • Cinti S (2018b) Obesity, type 2 diabetes and the adipose organ. Springer

    Book  Google Scholar 

  • Cinti S (2019) Anatomy and physiology of the nutritional system. Mol Asp Med 68:101–107

    Article  Google Scholar 

  • Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E et al (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46(11):2347–2355

    Article  CAS  PubMed  Google Scholar 

  • Cinti F, Mezza T, Severi I, Suleiman M, Cefalo CMA, Sorice GP et al (2021) Noradrenergic fibers are associated with beta-cell dedifferentiation and impaired beta-cell function in humans. Metabolism 114:154414

    Article  CAS  PubMed  Google Scholar 

  • Cohen P, Kajimura S (2021) The cellular and functional complexity of thermogenic fat. Nat Rev Mol Cell Biol 22(6):393–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colleluori G, Aguirre LE, Qualls C, Chen R, Napoli N, Villareal DT et al (2018a) Adipocytes ESR1 expression, body fat and response to testosterone therapy in hypogonadal men vary according to estradiol levels. Nutrients 10(9):1226

    Article  PubMed Central  Google Scholar 

  • Colleluori G, Chen R, Napoli N, Aguirre LE, Qualls C, Villareal DT et al (2018b) Fat mass follows a U-shaped distribution based on estradiol levels in postmenopausal women. Front Endocrinol (Lausanne) 9:315

    Article  Google Scholar 

  • Colleluori G, Perugini J, Barbatelli G, Cinti S (2021) Mammary gland adipocytes in lactation cycle, obesity and breast cancer. Rev Endocr Metab Disord 22(2):241–255

    Article  PubMed  PubMed Central  Google Scholar 

  • Cotillard A, Poitou C, Torcivia A, Bouillot JL, Dietrich A, Kloting N et al (2014) Adipocyte size threshold matters: link with risk of type 2 diabetes and improved insulin resistance after gastric bypass. J Clin Endocrinol Metab 99(8):E1466–E1470

    Article  CAS  PubMed  Google Scholar 

  • Cousin B, Cinti S, Morroni M, Raimbault S, Ricquier D, Penicaud L et al (1992) Occurrence of brown adipocytes in rat white adipose tissue: molecular and morphological characterization. J Cell Sci 103(Pt 4):931–942

    Article  CAS  PubMed  Google Scholar 

  • Cui X, Jing J, Wu R, Cao Q, Li F, Li K et al (2021) Adipose tissue-derived neurotrophic factor 3 regulates sympathetic innervation and thermogenesis in adipose tissue. Nat Commun 12(1):5362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elia E, Kessler SH, Kahn PA et al (2015) Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab 21(1):33–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Hollander EL, Bemelmans WJ, Boshuizen HC, Friedrich N, Wallaschofski H, Guallar-Castillon P et al (2012) The association between waist circumference and risk of mortality considering body mass index in 65- to 74-year-olds: a meta-analysis of 29 cohorts involving more than 58 000 elderly persons. Int J Epidemiol 41(3):805–817

    Article  PubMed  PubMed Central  Google Scholar 

  • De Matteis R, Cinti S (1998) Ultrastructural immunolocalization of leptin receptor in mouse brain. Neuroendocrinology 68(6):412–419

    Article  PubMed  Google Scholar 

  • De Matteis R, Arch JR, Petroni ML, Ferrari D, Cinti S, Stock MJ (2002) Immunohistochemical identification of the beta(3)-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine. Int J Obes Relat Metab Disord 26(11):1442–1450

    Article  PubMed  Google Scholar 

  • De Matteis R, Zingaretti MC, Murano I, Vitali A, Frontini A, Giannulis I et al (2009) In vivo physiological transdifferentiation of adult adipose cells. Stem Cells 27(11):2761–2768

    Article  PubMed  Google Scholar 

  • DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ et al (2015) Type 2 diabetes mellitus. Nat Rev Dis Primers 1:15019

    Article  PubMed  Google Scholar 

  • Despres JP, Lemieux I (2006) Abdominal obesity and metabolic syndrome. Nature 444(7121):881–887

    Article  CAS  PubMed  Google Scholar 

  • EASO (2020) In: Obesity EAftSo

    Google Scholar 

  • Frontini A, Rousset S, Cassard-Doulcier AM, Zingaretti C, Ricquier D, Cinti S (2007) Thymus uncoupling protein 1 is exclusive to typical brown adipocytes and is not found in thymocytes. J Histochem Cytochem 55(2):183–189

    Article  CAS  PubMed  Google Scholar 

  • Geserick M, Vogel M, Gausche R, Lipek T, Spielau U, Keller E et al (2018) Acceleration of BMI in early childhood and risk of sustained obesity. N Engl J Med 379(14):1303–1312

    Article  PubMed  Google Scholar 

  • Giannulis I, Mondini E, Cinti F, Frontini A, Murano I, Barazzoni R et al (2014) Increased density of inhibitory noradrenergic parenchymal nerve fibers in hypertrophic islets of Langerhans of obese mice. Nutr Metab Cardiovasc Dis 24(4):384–392

    Article  CAS  PubMed  Google Scholar 

  • Giordano A, Tonello C, Bulbarelli A, Cozzi V, Cinti S, Carruba MO et al (2002) Evidence for a functional nitric oxide synthase system in brown adipocyte nucleus. FEBS Lett 514(2–3):135–140

    Article  CAS  PubMed  Google Scholar 

  • Giordano A, Murano I, Mondini E, Perugini J, Smorlesi A, Severi I et al (2013) Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis. J Lipid Res 54(9):2423–2436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giordano A, Frontini A, Cinti S (2016) Convertible visceral fat as a therapeutic target to curb obesity. Nat Rev Drug Discov 15(6):405–424

    Article  CAS  PubMed  Google Scholar 

  • Giordano A, Perugini J, Kristensen DM, Sartini L, Frontini A, Kajimura S et al (2017) Mammary alveolar epithelial cells convert to brown adipocytes in post-lactating mice. J Cell Physiol 232(11):2923–2928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gnad T, Scheibler S, von Kugelgen I, Scheele C, Kilic A, Glode A et al (2014) Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors. Nature 516(7531):395–399

    Article  CAS  PubMed  Google Scholar 

  • Gnad T, Navarro G, Lahesmaa M, Reverte-Salisa L, Copperi F, Cordomi A et al (2020) Adenosine/A2B receptor signaling ameliorates the effects of aging and counteracts obesity. Cell Metab 32(1):56–70 e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goodpaster BH, Thaete FL, Kelley DE (2000) Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr 71(4):885–892

    Article  CAS  PubMed  Google Scholar 

  • Goossens GH, Bizzarri A, Venteclef N, Essers Y, Cleutjens JP, Konings E et al (2011) Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation. Circulation 124(1):67–76

    Article  CAS  PubMed  Google Scholar 

  • Guo W, Pirtskhalava T, Tchkonia T, Xie W, Thomou T, Han J et al (2007) Aging results in paradoxical susceptibility of fat cell progenitors to lipotoxicity. Am J Physiol Endocrinol Metab 292(4):E1041–E1051

    Article  CAS  PubMed  Google Scholar 

  • Hauser AS, Attwood MM, Rask-Andersen M, Schioth HB, Gloriam DE (2017) Trends in GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Discov 16(12):829–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K et al (2002) A central role for JNK in obesity and insulin resistance. Nature 420(6913):333–336

    Article  CAS  PubMed  Google Scholar 

  • Hotamisligil GS (2017) Inflammation, metaflammation and immunometabolic disorders. Nature 542(7640):177–185

    Article  CAS  PubMed  Google Scholar 

  • Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271(5249):665–668

    Article  CAS  PubMed  Google Scholar 

  • Isaac R, Reis FCG, Ying W, Olefsky JM (2021) Exosomes as mediators of intercellular crosstalk in metabolism. Cell Metab 33(9):1744–1762

    Article  CAS  PubMed  Google Scholar 

  • Jeffery E, Wing A, Holtrup B, Sebo Z, Kaplan JL, Saavedra-Pena R et al (2016) The adipose tissue microenvironment regulates depot-specific adipogenesis in obesity. Cell Metab 24(1):142–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karlstedt K, Ahman MJ, Anichtchik OV, Soinila S, Panula P (2003) Expression of the H3 receptor in the developing CNS and brown fat suggests novel roles for histamine. Mol Cell Neurosci 24(3):614–622

    Article  CAS  PubMed  Google Scholar 

  • Kim SM, Lun M, Wang M, Senyo SE, Guillermier C, Patwari P et al (2014) Loss of white adipose hyperplastic potential is associated with enhanced susceptibility to insulin resistance. Cell Metab 20(6):1049–1058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klepac K, Kilic A, Gnad T, Brown LM, Herrmann B, Wilderman A et al (2016) The Gq signalling pathway inhibits brown and beige adipose tissue. Nat Commun 7:10895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kotzbeck P, Giordano A, Mondini E, Murano I, Severi I, Venema W et al (2018) Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation. J Lipid Res 59(5):784–794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larsen TM, Toubro S, van Baak MA, Gottesdiener KM, Larson P, Saris WH et al (2002) Effect of a 28-d treatment with L-796568, a novel beta(3)-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am J Clin Nutr 76(4):780–788

    Article  CAS  PubMed  Google Scholar 

  • Le KA, Mahurkar S, Alderete TL, Hasson RE, Adam TC, Kim JS et al (2011) Subcutaneous adipose tissue macrophage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kappaB stress pathway. Diabetes 60(11):2802–2809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JS, Kim SH, Jun DW, Han JH, Jang EC, Park JY et al (2009) Clinical implications of fatty pancreas: correlations between fatty pancreas and metabolic syndrome. World J Gastroenterol 15(15):1869–1875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee YH, Petkova AP, Mottillo EP, Granneman JG (2012) In vivo identification of bipotential adipocyte progenitors recruited by beta3-adrenoceptor activation and high-fat feeding. Cell Metab 15(4):480–491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Look ARG (2014) Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD study. Obesity (Silver Spring) 22(1):5–13

    Article  Google Scholar 

  • Look ARG, Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM et al (2013) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369(2):145–154

    Article  Google Scholar 

  • Lumeng CN, Liu J, Geletka L, Delaney C, Delproposto J, Desai A et al (2011) Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. J Immunol 187(12):6208–6216

    Article  CAS  PubMed  Google Scholar 

  • Nechad M (1986) Structure and development of brown adipose tissue. Edward Arnold, London

    Google Scholar 

  • Marcelin G, Ferreira A, Liu Y, Atlan M, Aron-Wisnewsky J, Pelloux V et al (2017) A PDGFRalpha-mediated switch toward CD9(high) adipocyte progenitors controls obesity-induced adipose tissue fibrosis. Cell Metab 25(3):673–685

    Article  CAS  PubMed  Google Scholar 

  • Morroni M, Giordano A, Zingaretti MC, Boiani R, De Matteis R, Kahn BB et al (2004) Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland. Proc Natl Acad Sci U S A 101(48):16801–16806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muller S, Kulenkampff E, Wolfrum C (2016) Adipose tissue stem cells. Handb Exp Pharmacol 233:251–263

    Article  CAS  PubMed  Google Scholar 

  • Murano I, Barbatelli G, Parisani V, Latini C, Muzzonigro G, Castellucci M et al (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 49(7):1562–1568

    Article  CAS  PubMed  Google Scholar 

  • NCD-RisC. Adult Body Mass Index, visited on March 2021. https://www.ncdrisc.org/data-visualisations-adiposity.html

  • O'Mara AE, Johnson JW, Linderman JD, Brychta RJ, McGehee S, Fletcher LA et al (2020) Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. J Clin Invest 130(5):2209–2219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pasquali R, Casanueva F, Haluzik M, van Hulsteijn L, Ledoux S, Monteiro MP et al (2020) European Society of Endocrinology clinical practice guideline: endocrine work-up in obesity. Eur J Endocrinol 182(1):G1–G32

    Article  CAS  PubMed  Google Scholar 

  • Redman LM, de Jonge L, Fang X, Gamlin B, Recker D, Greenway FL et al (2007) Lack of an effect of a novel beta3-adrenoceptor agonist, TAK-677, on energy metabolism in obese individuals: a double-blind, placebo-controlled randomized study. J Clin Endocrinol Metab 92(2):527–531

    Article  CAS  PubMed  Google Scholar 

  • Roberts LD, Ashmore T, Kotwica AO, Murfitt SA, Fernandez BO, Feelisch M et al (2015) Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway. Diabetes 64(2):471–484

    Article  CAS  PubMed  Google Scholar 

  • Rodeheffer MS, Birsoy K, Friedman JM (2008) Identification of white adipocyte progenitor cells in vivo. Cell 135(2):240–249

    Article  CAS  PubMed  Google Scholar 

  • Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F et al (2016) Asprosin, a fasting-induced glucogenic protein hormone. Cell 165(3):566–579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosen ED, Spiegelman BM (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444(7121):847–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenwald M, Perdikari A, Rulicke T, Wolfrum C (2013) Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol 15(6):659–667

    Article  CAS  PubMed  Google Scholar 

  • Rouault C, Marcelin G, Adriouch S, Rose C, Genser L, Ambrosini M et al (2021) Senescence-associated beta-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity. Diabetologia 64(1):240–254

    Article  CAS  PubMed  Google Scholar 

  • Salans LB, Horton ES, Sims EA (1971) Experimental obesity in man: cellular character of the adipose tissue. J Clin Invest 50(5):1005–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santanasto AJ, Goodpaster BH, Kritchevsky SB, Miljkovic I, Satterfield S, Schwartz AV et al (2017) Body composition remodeling and mortality: the health aging and body composition study. J Gerontol A Biol Sci Med Sci 72(4):513–519

    PubMed  Google Scholar 

  • Sarvari AK, Van Hauwaert EL, Markussen LK, Gammelmark E, Marcher AB, Ebbesen MF et al (2021) Plasticity of epididymal adipose tissue in response to diet-induced obesity at single-nucleus resolution. Cell Metab 33(2):437–53.e5

    Article  CAS  PubMed  Google Scholar 

  • Sepe A, Tchkonia T, Thomou T, Zamboni M, Kirkland JL (2011) Aging and regional differences in fat cell progenitors - a mini-review. Gerontology 57(1):66–75

    Article  PubMed  Google Scholar 

  • Shan T, Liang X, Bi P, Zhang P, Liu W, Kuang S (2013) Distinct populations of adipogenic and myogenic Myf5-lineage progenitors in white adipose tissues. J Lipid Res 54(8):2214–2224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siervo M, Lara J, Celis-Morales C, Vacca M, Oggioni C, Battezzati A et al (2016) Age-related changes in basal substrate oxidation and visceral adiposity and their association with metabolic syndrome. Eur J Nutr 55(4):1755–1767

    Article  CAS  PubMed  Google Scholar 

  • Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O et al (2008) Dynamics of fat cell turnover in humans. Nature 453(7196):783–787

    Article  CAS  PubMed  Google Scholar 

  • Sun K, Tordjman J, Clement K, Scherer PE (2013) Fibrosis and adipose tissue dysfunction. Cell Metab 18(4):470–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun W, Dong H, Balaz M, Slyper M, Drokhlyansky E, Colleluori G, Giordano A, Kovanicova Z, Stefanicka P, Ding L, Rudofsky G, Ukropec J, Cinti S, Regev A, Wolfrum C (2020) Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis. Nature. https://doi.org/10.1101/2020.01.20.890327

  • Tchkonia T, Thomou T, Zhu Y, Karagiannides I, Pothoulakis C, Jensen MD et al (2013) Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab 17(5):644–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toplak H, Woodward E, Yumuk V, Oppert JM, Halford JC, Fruhbeck G (2015) 2014 EASO position statement on the use of anti-obesity drugs. Obes Facts 8(3):166–174

    Article  PubMed  PubMed Central  Google Scholar 

  • Tran KV, Gealekman O, Frontini A, Zingaretti MC, Morroni M, Giordano A et al (2012) The vascular endothelium of the adipose tissue gives rise to both white and brown fat cells. Cell Metab 15(2):222–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vitali A, Murano I, Zingaretti MC, Frontini A, Ricquier D, Cinti S (2012) The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytes. J Lipid Res 53(4):619–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang QA, Tao C, Gupta RK, Scherer PE (2013) Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 19(10):1338–1344

    Article  PubMed  PubMed Central  Google Scholar 

  • Ward ZJ, Bleich SN, Cradock AL, Barrett JL, Giles CM, Flax C et al (2019) Projected U.S. state-level prevalence of adult obesity and severe obesity. N Engl J Med 381(25):2440–2450

    Article  PubMed  Google Scholar 

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112(12):1796–1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE (2000) Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia 43(12):1498–1506

    Article  CAS  PubMed  Google Scholar 

  • WHO (2021a) WHO European Childhood Obesity Surveillance Initiative (COSI) Report on the fourth round of data collection, 2015–2017. https://www.euro.who.int/en/health-topics/disease-prevention/nutrition/activities/who-european-childhood-obesity-surveillance-initiative-cosi/cosi-publications/who-european-childhood-obesity-surveillance-initiative-cosi-report-on-the-fourth-round-of-data-collection,-20152017-2021

  • WHO (2021b) Obesity report. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

  • Wolf Y, Boura-Halfon S, Cortese N, Haimon Z, Sar Shalom H, Kuperman Y et al (2017) Brown-adipose-tissue macrophages control tissue innervation and homeostatic energy expenditure. Nat Immunol 18(6):665–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H, Ballantyne CM (2017) Skeletal muscle inflammation and insulin resistance in obesity. J Clin Invest 127(1):43–54

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112(12):1821–1830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan C, Zeng T, Lee K, Nobis M, Loh K, Gou L et al (2021) Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity. Nat Commun 12(1):2622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ying W, Lee YS, Dong Y, Seidman JS, Yang M, Isaac R et al (2019) Expansion of islet-resident macrophages leads to inflammation affecting beta cell proliferation and function in obesity. Cell Metab 29(2):457–74.e5

    Article  CAS  PubMed  Google Scholar 

  • Ying W, Gao H, Dos Reis FCG, Bandyopadhyay G, Ofrecio JM, Luo Z et al (2021) MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metab 33(4):781–90.e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505):425–432

    Article  CAS  PubMed  Google Scholar 

  • Zhao YX, Pan JB, Wang YN, Zou Y, Guo L, Tang QQ et al (2019) Stimulation of histamine H4 receptor participates in cold-induced browning of subcutaneous white adipose tissue. Am J Physiol Endocrinol Metab 317(6):E1158–E1E71

    Article  CAS  PubMed  Google Scholar 

  • Zimmerlin L, Donnenberg VS, Rubin JP, Donnenberg AD (2013) Mesenchymal markers on human adipose stem/progenitor cells. Cytometry A 83(1):134–140

    Article  PubMed  Google Scholar 

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Acknowledgments

Fondo Integrativo Speciale per la Ricerca from the Italian Ministry of University and Research; grant number: FISR2020IP_05217, Progetti di Rilevante Interesse Nazionale (PRIN 2017, #2017L8Z2).

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Authors have nothing to disclose.

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Authors and Affiliations

  1. Department of Experimental and Clinical Medicine, Center of Obesity, Marche Polytechnic University, Ancona, Italy

    Georgia Colleluori, Jessica Perugini, Antonio Giordano & Saverio Cinti

Authors
  1. Georgia Colleluori
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  2. Jessica Perugini
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  3. Antonio Giordano
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  4. Saverio Cinti
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Correspondence to Saverio Cinti .

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Editors and Affiliations

  1. Institute for Clinical Diabetology, German Diabetes Center, Düsseldorf, Germany

    Juergen Eckel

  2. NutriOmique Research group, Nutrition Department, Pitié-Salpêtrière Hospital, APHP, Sorbonne Université/INSERM, Paris, France

    Karine Clément

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Colleluori, G., Perugini, J., Giordano, A., Cinti, S. (2022). From Obesity to Diabetes: The Role of the Adipose Organ. In: Eckel, J., Clément, K. (eds) From Obesity to Diabetes. Handbook of Experimental Pharmacology, vol 274. Springer, Cham. https://doi.org/10.1007/164_2021_572

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