Obesity-associated improvements in metabolic profile through expansion of adipose tissue

Ja Young Kim, Esther Van De Wall, Mathieu Laplante, Anthony Azzara, Maria E. Trujillo, Susanna M. Hofmann, Todd Schraw, Jorge L. Durand, Hua Li, Guangyu Li, Linda A. Jelicks, Mark F. Mehler, David Y. Hui, Yves Deshaies, Gerald I. Shulman, Gary J. Schwartz, Philipp E. Scherer

Research output: Contribution to journalArticle

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Abstract

Excess caloric intake can lead to insulin resistance. The underlying reasons are complex but likely related to ectopic lipid deposition in nonadipose tissue. We hypothesized that the inability to appropriately expand subcutaneous adipose tissue may be an underlying reason for insulin resistance and β cell failure. Mice lacking leptin while overexpressing adiponectin showed normalized glucose and insulin levels and dramatically improved glucose as well as positively affected serum triglyceride levels. Therefore, modestly increasing the levels of circulating full-length adiponectin completely rescued the diabetic phenotype in ob/ob mice. They displayed increased expression of PPARγ target genes and a reduction in macrophage infiltration in adipose tissue and systemic inflammation. As a result, the transgenic mice were morbidly obese, with significantly higher levels of adipose tissue than their ob/ob littermates, leading to an interesting dichotomy of increased fat mass associated with improvement in insulin sensitivity. Based on these data, we propose that adiponectin acts as a peripheral "starvation" signal promoting the storage of triglycerides preferentially in adipose tissue. As a consequence, reduced triglyceride levels in the liver and muscle convey improved systemic insulin sensitivity. These mice therefore represent what we believe is a novel model of morbid obesity associated with an improved metabolic profile.

Original languageEnglish (US)
Pages (from-to)2621-2637
Number of pages17
JournalJournal of Clinical Investigation
Volume117
Issue number9
DOIs
StatePublished - Sep 4 2007

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Metabolome
Insulin Resistance
Adipose Tissue
Adiponectin
Obesity
Triglycerides
Glucose
Peroxisome Proliferator-Activated Receptors
Morbid Obesity
Subcutaneous Fat
Starvation
Leptin
Energy Intake
Transgenic Mice
Fats
Macrophages
Insulin
Inflammation
Phenotype
Lipids

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kim, J. Y., Van De Wall, E., Laplante, M., Azzara, A., Trujillo, M. E., Hofmann, S. M., ... Scherer, P. E. (2007). Obesity-associated improvements in metabolic profile through expansion of adipose tissue. Journal of Clinical Investigation, 117(9), 2621-2637. https://doi.org/10.1172/JCI31021

Obesity-associated improvements in metabolic profile through expansion of adipose tissue. / Kim, Ja Young; Van De Wall, Esther; Laplante, Mathieu; Azzara, Anthony; Trujillo, Maria E.; Hofmann, Susanna M.; Schraw, Todd; Durand, Jorge L.; Li, Hua; Li, Guangyu; Jelicks, Linda A.; Mehler, Mark F.; Hui, David Y.; Deshaies, Yves; Shulman, Gerald I.; Schwartz, Gary J.; Scherer, Philipp E.

In: Journal of Clinical Investigation, Vol. 117, No. 9, 04.09.2007, p. 2621-2637.

Research output: Contribution to journalArticle

Kim, JY, Van De Wall, E, Laplante, M, Azzara, A, Trujillo, ME, Hofmann, SM, Schraw, T, Durand, JL, Li, H, Li, G, Jelicks, LA, Mehler, MF, Hui, DY, Deshaies, Y, Shulman, GI, Schwartz, GJ & Scherer, PE 2007, 'Obesity-associated improvements in metabolic profile through expansion of adipose tissue', Journal of Clinical Investigation, vol. 117, no. 9, pp. 2621-2637. https://doi.org/10.1172/JCI31021
Kim JY, Van De Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. Journal of Clinical Investigation. 2007 Sep 4;117(9):2621-2637. https://doi.org/10.1172/JCI31021
Kim, Ja Young ; Van De Wall, Esther ; Laplante, Mathieu ; Azzara, Anthony ; Trujillo, Maria E. ; Hofmann, Susanna M. ; Schraw, Todd ; Durand, Jorge L. ; Li, Hua ; Li, Guangyu ; Jelicks, Linda A. ; Mehler, Mark F. ; Hui, David Y. ; Deshaies, Yves ; Shulman, Gerald I. ; Schwartz, Gary J. ; Scherer, Philipp E. / Obesity-associated improvements in metabolic profile through expansion of adipose tissue. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 9. pp. 2621-2637.
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