Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting

Michael W. Rajala, Yong Qi, Hiral R. Patel, Nobuhiko Takahashi, Ronadip Banerjee, Utpal B. Pajvani, Madhur K. Sinha, Ronald L. Gingerich, Philipp E. Scherer, Rexford S. Ahima

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Abstract

Resistin was originally reported as an adipose tissue-specific hormone that provided a link between obesity and diabetes. Resistin protein level was elevated in obese mice and decreased by insulin-sensitizing thiazolidinediones. Immunoneutralization of resistin improved insulin sensitivity in diet-induced obese mice, while the administration of exogenous resistin induced insulin resistance. More recently, we have shown that ablation of the resistin gene in mice decreased fasting glucose through impairment of gluconeogenesis, while resistin treatment in these knockout mice increased hepatic glucose production. However, the link between resistin and glucose homeostasis has been questioned by studies demonstrating reduced, rather than increased, resistin mRNA expression in obese and diabetic mice. To better understand the regulation of resistin, we developed a sensitive and specific RIA resistin that could accurately measure serum resistin levels in several mouse models. We show that while resistin mRNA is indeed suppressed in obese mice, the circulating resistin level is significantly elevated and positively correlated with insulin, glucose, and lipids. Both resistin mRNA expression and protein levels in Lepob/ob mice are suppressed by leptin treatment in parallel with reductions in glucose and insulin. In wild-type mice, serum resistin increases after nocturnal feeding, concordant with rising levels of insulin. Resistin mRNA and protein levels decline in parallel with glucose and insulin during fasting and are restored after refeeding. We performed clamp studies to determine whether resistin is causally related to insulin and glucose. Adipose resistin expression and serum resistin increased in response to hyperinsulinemia and further in response to hyperglycemia. Taken together, these findings suggest that the nutritional regulation of resistin and changes in resistin gene expression and circulating levels in obesity are mediated, at least in part, through insulin and glucose.

Original languageEnglish (US)
Pages (from-to)1671-1679
Number of pages9
JournalDiabetes
Volume53
Issue number7
DOIs
StatePublished - Jul 2004

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Resistin
Fasting
Obesity
Glucose
Obese Mice
Insulin
Messenger RNA
Insulin Resistance
Serum
Thiazolidinediones

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Rajala, M. W., Qi, Y., Patel, H. R., Takahashi, N., Banerjee, R., Pajvani, U. B., ... Ahima, R. S. (2004). Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes, 53(7), 1671-1679. https://doi.org/10.2337/diabetes.53.7.1671

Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. / Rajala, Michael W.; Qi, Yong; Patel, Hiral R.; Takahashi, Nobuhiko; Banerjee, Ronadip; Pajvani, Utpal B.; Sinha, Madhur K.; Gingerich, Ronald L.; Scherer, Philipp E.; Ahima, Rexford S.

In: Diabetes, Vol. 53, No. 7, 07.2004, p. 1671-1679.

Research output: Contribution to journalArticle

Rajala, MW, Qi, Y, Patel, HR, Takahashi, N, Banerjee, R, Pajvani, UB, Sinha, MK, Gingerich, RL, Scherer, PE & Ahima, RS 2004, 'Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting', Diabetes, vol. 53, no. 7, pp. 1671-1679. https://doi.org/10.2337/diabetes.53.7.1671
Rajala MW, Qi Y, Patel HR, Takahashi N, Banerjee R, Pajvani UB et al. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes. 2004 Jul;53(7):1671-1679. https://doi.org/10.2337/diabetes.53.7.1671
Rajala, Michael W. ; Qi, Yong ; Patel, Hiral R. ; Takahashi, Nobuhiko ; Banerjee, Ronadip ; Pajvani, Utpal B. ; Sinha, Madhur K. ; Gingerich, Ronald L. ; Scherer, Philipp E. ; Ahima, Rexford S. / Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. In: Diabetes. 2004 ; Vol. 53, No. 7. pp. 1671-1679.
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