| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 20, 2005
Accepted on January 27, 2006
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, 70808
* To whom correspondence should be addressed. E-mail: butleraa{at}pbrc.edu.
Loss of brain melanocortin receptors (Mc3rKO, Mc4rKO) causes increased adiposity and exacerbates diet-induced obesity (DIO). Little is known about how Mc3r or Mc4r genotype, diet and obesity affect insulin sensitivity. Insulin resistance, assessed by insulin and glucose tolerance tests, Ser307 phosphorylation of insulin receptor substrate 1, and activation of protein kinase B, was examined in control and DIO wild-type (WT), Mc3rKO and Mc4rKO C57BL/6J mice. Mc4rKO mice were hyperphagic and had increased metabolic efficiency (weight gain/kJ consumed) relative to WT; both parameters increased further on high fat diet. Obesity of Mc3rKO was more dependent on fat intake, involving increased metabolic efficiency. Fat mass of DIO Mc3rKO and Mc4rKO was similar, although Mc4rKO gained weight more rapidly. Mc4rKO develop hepatic insulin resistance and severe hepatic steatosis with obesity, independent of diet. DIO caused further deterioration of insulin action in Mc4rKO of either sex, and in male Mc3rKO, compared with controls, associated with increased fasting insulin, severe glucose intolerance, and reduced insulin signaling in muscle and adipose. DIO female Mc3rKO exhibited very modest perturbations in glucose metabolism and insulin sensitivity. Consistent with previous data suggesting impaired fat oxidation, both Mc3rKO and Mc4rKO had reduced muscle oxidative metabolism, a risk factor for weight gain and insulin resistance. Energy expenditure was, however, increased in Mc4rKO compared with Mc3rKO and controls, perhaps due to hyperphagia and metabolic costs associated with rapid growth. In summary, DIO affects insulin sensitivity more severely in Mc4rKO compared with Mc3rKO, perhaps due to a more positive energy balance.
This article has been cited by other articles:
 |
|
 |
|
  N. C. Bingham, K. K. Anderson, A. L. Reuter, N. R. Stallings, and K. L. Parker Selective Loss of Leptin Receptors in the Ventromedial Hypothalamic Nucleus Results in Increased Adiposity and a Metabolic Syndrome Endocrinology, May 1, 2008; 149(5): 2138 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Trevaskis, E. A. Meyer, J. E. Galgani, and A. A. Butler Counterintuitive Effects of Double-Heterozygous Null Melanocortin-4 Receptor and Leptin Genes on Diet-Induced Obesity and Insulin Resistance in C57BL/6J Mice Endocrinology, January 1, 2008; 149(1): 174 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. J. Ellacott, J. G. Murphy, D. L. Marks, and R. D. Cone Obesity-Induced Inflammation in White Adipose Tissue Is Attenuated by Loss of Melanocortin-3 Receptor Signaling Endocrinology, December 1, 2007; 148(12): 6186 - 6194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shimizu, K. Inoue, and M. Mori The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure J. Endocrinol., April 1, 2007; 193(1): 1 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Santoro, L. Perrone, G. Cirillo, P. Raimondo, A. Amato, C. Brienza, and E. M. del Giudice Effect of the melanocortin-3 receptor C17A and G241A variants on weight loss in childhood obesity Am. J. Clinical Nutrition, April 1, 2007; 85(4): 950 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Cone Studies on the Physiological Functions of the Melanocortin System Endocr. Rev., December 1, 2006; 27(7): 736 - 749. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
