Resistin’s, obesity and insulin resistance: the continuing disconnect between rodents and humans
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This review aimed to discuss the conflicting findings from resistin research in rodents and humans as well as recent advances in our understanding of resistin’s role in obesity and insulin resistance.
A comprehensive review and synthesis of resistin’s role in obesity and insulin resistance as well as conflicting findings from resistin research in rodents and humans.
In rodents, resistin is increased in high-fat/high-carbohydrate-fed, obese states characterized by impaired glucose uptake and insulin sensitivity. Resistin plays a causative role in the development of insulin resistance in rodents via 5′ AMP-activated protein kinase (AMPK)-dependent and AMPK-independent suppressor of cytokine signaling-3 (SOCS-3) signaling. In contrast to rodents, human resistin is primarily secreted by peripheral-blood mononuclear cells (PBMCs) as opposed to white adipocytes. Circulating resistin levels have been positively associated with central/visceral obesity (but not BMI) as well as insulin resistance, while other studies show no such association. Human resistin has a role in pro-inflammatory processes that have been conclusively associated with obesity and insulin resistance. PBMCs, as well as vascular cells, have been identified as the primary targets of resistin’s pro-inflammatory activity via nuclear factor-κB (NF-κB, p50/p65) and other signaling pathways.
Mounting evidence reveals a continuing disconnect between resistin’s role in rodents and humans due to significant differences between these two species with respect to resistin’s gene and protein structure, differential gene regulation, tissue-specific distribution, and insulin resistance induction as well as a paucity of evidence regarding the resistin receptor and downstream signaling mechanisms of action.
KeywordsAdipocyte Adipocytokine Adipokine Insulin Obesity Resistin
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Conflict of interest
The authors state that they have no conflict of interest to declare.
This article does not contain any studies with human participants or animal performed by any of the authors.
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- 8.Asensio C, Cettour-Rose P, Theander-Carrillo C, Rohner-Jeanrenaud F, Muzzin P (2004) Changes in glycemia by leptin administration or high-fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis. Endocrinology 145:2206–2213PubMedCrossRefGoogle Scholar
- 18.Cherneva RV, Georgiev OB, Petrova DS, Mondeshki TL, Ruseva SR, Cakova AD et al. (2013) Resistin-the link between adipose tissue dysfunction and insulin resistance in patients with obstructive sleep apnea. J Diabetes Metab Disord 12Google Scholar
- 45.Kwon H, Pessin JE (2013) Adipokines mediate inflammation and insulin resistance Front Endocrinol 4Google Scholar
- 49.Lee JH, Chan JL, Yiannakouris N, Kontogianni M, Estrada E, Seip R et al (2003) Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab 88:4848–4856PubMedCrossRefGoogle Scholar
- 52.Li Y, Ding L, Hassan W, Abdelkader D, Shang J (2013) Adipokines and hepatic insulin resistance. J Diab Res 2013Google Scholar
- 77.Osawa H, Tabara Y, Kawamoto R, Ohashi J, Ochi M, Onuma H et al (2007) Plasma resistin, associated with single nucleotide polymorphism −420, is correlated with insulin resistance, lower HDL cholesterol, and high-sensitivity C-reactive protein in the Japanese general population. Diab Care 30:1501–1506CrossRefGoogle Scholar
- 94.Seo JB, Noh MJ, Yoo EJ, Park SY, Park J, Lee IK et al (2003) Functional characterization of the human resistin promoter with adipocyte determination-and differentiation-dependent factor 1/sterol regulatory element binding protein 1c and CCAAT enhancer binding protein-α. Mol Endocrinol 17:1522–1533PubMedCrossRefGoogle Scholar
- 95.Sheng CH, Du ZW, Song Y, Wu XD, Zhang YC, Wu M, et al. (2013) Human resistin inhibits myogenic differentiation and induces insulin resistance in myocytes. BioMed Res Int 2013Google Scholar
- 115.Yannakoulia M, Yiannakouris N, Blüher S, Matalas A-L, Klimis-Zacas D, Mantzoros CS (2003) Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metab 88:1730–1736PubMedCrossRefGoogle Scholar
- 116.Youn B-S, Yu K-Y, Park HJ, Lee NS, Min SS, Youn MY et al (2004) Plasma resistin concentrations measured by enzyme-linked immunosorbent assay using a newly developed monoclonal antibody are elevated in individuals with type 2 diabetes mellitus. J Clin Endocrinol Metab 89:150–156PubMedCrossRefGoogle Scholar