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Adropin deficiency is associated with increased adiposity and insulin resistance

Academic Article
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Overview

authors

  • Kumar, K. G.
  • Zhang, J. Y.
  • Gao, S.
  • Rossi, J.
  • McGuinness, O. P.
  • Halem, H. H.
  • Culler, M. D.
  • Mynatt, R. L.
  • Butler, Andrew

publication date

  • July 2012

journal

  • Obesity  Journal

abstract

  • Adropin is a secreted peptide that improves hepatic steatosis and glucose homeostasis when administered to diet-induced obese mice. It is not clear if adropin is a peptide hormone regulated by signals of metabolic state. Moreover, the significance of a decline in adropin expression with obesity with respect to metabolic disease is also not clear. We investigated the regulation of serum adropin by metabolic status and diet. Serum adropin levels were high in chow-fed conditions and were suppressed by fasting and diet-induced obesity (DIO). High adropin levels were observed in mice fed a high-fat low carbohydrate diet, whereas lower levels were observed in mice fed a low-fat high carbohydrate diet. To investigate the role of adropin deficiency in metabolic homeostasis, we generated adropin knockout mice (AdrKO) on the C57BL/6J background. AdrKO displayed a 50%-increase in increase in adiposity, although food intake and energy expenditure were normal. AdrKO also exhibited dyslipidemia and impaired suppression of endogenous glucose production (EndoR(a)) in hyperinsulinemic-euglycemic clamp conditions, suggesting insulin resistance. While homo- and heterozygous carriers of the null adropin allele exhibited normal DIO relative to controls, impaired glucose tolerance associated with weight gain was more severe in both groups. In summary, adropin is a peptide hormone regulated by fasting and feeding. In fed conditions, adropin levels are regulated dietary macronutrients, and increase with dietary fat content. Adropin is not required for regulating food intake, however, its functions impact on adiposity and are involved in preventing insulin resistance, dyslipidemia, and impaired glucose tolerance.

subject areas

  • Adiposity
  • Animals
  • Axonemal Dyneins
  • Blood Glucose
  • Dietary Carbohydrates
  • Dietary Fats
  • Dyslipidemias
  • Eating
  • Energy Metabolism
  • Fasting
  • Fatty Liver
  • Female
  • Glucose Clamp Technique
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteins
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Identity

PubMed Central ID

  • PMC3905465

International Standard Serial Number (ISSN)

  • 1930-7381

Digital Object Identifier (DOI)

  • 10.1038/oby.2012.31

PubMed ID

  • 22318315
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Additional Document Info

start page

  • 1394

end page

  • 1402

volume

  • 20

issue

  • 7

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