Agouti Expression in Human Adipose Tissue

Functional Consequences and Increased Expression in Type 2 Diabetes

  1. Steven R. Smith1,
  2. Barbara Gawronska-Kozak1,
  3. Lenka Janderová1,
  4. Taylor Nguyen1,
  5. Angela Murrell1,
  6. Jacqueline M. Stephens2 and
  7. Randall L. Mynatt1
  1. 1Pennington Biomedical Research Center, Baton Rouge, Louisiana
  2. 2Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana
  1. Address correspondence and reprint requests to Randall L. Mynatt Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808. E-mail: mynattrl{at}


It is well recognized that the agouti/melanocortin system is an important regulator of body weight homeostasis. Given that agouti is expressed in human adipose tissue and that the ectopic expression of agouti in adipose tissue results in moderately obese mice, the link between agouti expression in human adipose tissue and obesity/type 2 diabetes was investigated. Although there was no apparent relationship between agouti mRNA levels and BMI, agouti mRNA levels were significantly elevated in subjects with type 2 diabetes. The regulation of agouti in cultured human adipocytes revealed that insulin did not regulate agouti mRNA, whereas dexamethasone treatment potently increased the levels of agouti mRNA. Experiments with cultured human preadipocytes and with cells obtained from transgenic mice that overexpress agouti demonstrated that melanocortin receptor (MCR) signaling in adipose tissue can regulate both preadipocyte proliferation and differentiation. Taken together, these results reveal that agouti can regulate adipogenesis at several levels and suggest that there are functional consequences of elevated agouti levels in human adipose tissue. The influence of MCR signaling on adipogenesis combined with the well-established role of MCR signaling in the hypothalamus suggest that adipogenesis is coordinately regulated with food intake and energy expenditure.


    • Accepted August 25, 2003.
    • Received March 13, 2003.
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