Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities

Babak Razani, Terry P. Combs, Xiao Bo Wang, Philippe G. Frank, David S. Park, Robert G. Russell, Maomi Li, Baiyu Tang, Linda A. Jelicks, Philipp E. Scherer, Michael P. Lisanti

Research output: Contribution to journalArticle

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Abstract

Caveolae organelles and caveolin-1 protein expression are most abundant in adipocytes and endothelial cells. Our initial report on mice lacking caveolin-1 (Cav-1) demonstrated a loss of caveolae and perturbations in endothelial cell function. More recently, however, observation of the Cav-1-deficient cohorts into old age revealed significantly lower body weights, as compared with wild-type controls. These results suggest that Cav-1 null mice may have problems with lipid metabolism and/or adipocyte functioning. To test this hypothesis directly, we placed a cohort of wild-type and Cav-1 null mice on a high fat diet. Interestingly, despite being hyperphagic, Cav-1 null mice show overt resistance to diet-induced obesity. As predicted, adipocytes from Cav-1 null null mice lack caveolae membranes. Early on, a lack of caveolin-1 selectively affects only the female mammary gland fat pad and results in a near complete ablation of the hypo-dermal fat layer. There are also indications of generalized adipose tissue pathology. With increasing age, a systemic decompensation in lipid accumulation occurs resulting in dramatically smaller fat pads, histologically reduced adipocyte cell diameter, and a poorly differentiated/hypercellular white adipose parenchyma. To gain mechanistic insights into this phenotype, we show that, although serum insulin, glucose, and cholesterol levels are entirely normal, Cav-1 null mice have severely elevated triglyceride and free fatty acid levels, especially in the postprandial state. However, this build-up of triglyceriderich chylomicrons/very low density lipoproteins is not due to perturbed lipoprotein lipase activity, a major culprit of isolated hypertriglyceridemia. The lean body phenotype and metabolic defects observed in Cav-1 null mice are consistent with the previously proposed functions of caveolin-1 and caveolae in adipocytes. Our results show for the first time a clear role for caveolins in systemic lipid homeostasis in vivo and place caveolin-1/ caveolae as major factors in hyperlipidemias and obesity.

Original languageEnglish (US)
Pages (from-to)8635-8647
Number of pages13
JournalJournal of Biological Chemistry
Volume277
Issue number10
DOIs
StatePublished - Mar 8 2002

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Caveolin 1
Hypertriglyceridemia
Nutrition
Adipocytes
Obesity
Diet
Caveolae
Fats
Caveolins
Adipose Tissue
Endothelial cells
Endothelial Cells
Phenotype
Lipids
Chylomicrons
VLDL Lipoproteins
Lipoprotein Lipase
High Fat Diet
Pathology
Human Mammary Glands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Razani, B., Combs, T. P., Wang, X. B., Frank, P. G., Park, D. S., Russell, R. G., ... Lisanti, M. P. (2002). Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. Journal of Biological Chemistry, 277(10), 8635-8647. https://doi.org/10.1074/jbc.M110970200

Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. / Razani, Babak; Combs, Terry P.; Wang, Xiao Bo; Frank, Philippe G.; Park, David S.; Russell, Robert G.; Li, Maomi; Tang, Baiyu; Jelicks, Linda A.; Scherer, Philipp E.; Lisanti, Michael P.

In: Journal of Biological Chemistry, Vol. 277, No. 10, 08.03.2002, p. 8635-8647.

Research output: Contribution to journalArticle

Razani, B, Combs, TP, Wang, XB, Frank, PG, Park, DS, Russell, RG, Li, M, Tang, B, Jelicks, LA, Scherer, PE & Lisanti, MP 2002, 'Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities', Journal of Biological Chemistry, vol. 277, no. 10, pp. 8635-8647. https://doi.org/10.1074/jbc.M110970200
Razani, Babak ; Combs, Terry P. ; Wang, Xiao Bo ; Frank, Philippe G. ; Park, David S. ; Russell, Robert G. ; Li, Maomi ; Tang, Baiyu ; Jelicks, Linda A. ; Scherer, Philipp E. ; Lisanti, Michael P. / Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 10. pp. 8635-8647.
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AU - Park, David S.

AU - Russell, Robert G.

AU - Li, Maomi

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