Caveolin-1-deficient Mice Are Lean, Resistant to Diet-induced Obesity, and Show Hypertriglyceridemia with Adipocyte Abnormalities*

By B. Razani, Terry P. Combs, Xiao Bo Wang, P. G. Frank, David S. Park, R. Russell, Maomi Li, Baiyu Tang, L. Jelicks, P. Scherer and 1 more. Journal of Biological Chemistry, 2002

599 citations recorded by the source corpus.

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 post-prandial state. However, this build-up of triglyceride-rich 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.

Subfields: Cardiology and Cardiovascular Medicine, Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8e1f88df3928720c3439ac3e821e9080e46496dc

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

1. P. Scherer
2. Haiming Cao
3. M. Blüher

In Cell Biology

1. Robert G. Parton
2. K. Simons
3. P. Scherer
4. M. Trujillo
5. M. Lisanti
6. C. Dart
7. G. Nicolson
8. John Hancock

In Molecular Biology

1. Robert G. Parton
2. K. Simons
3. M. Trujillo
4. P. Scherer
5. C. Dart
6. G. Nicolson
7. John Hancock
8. Elina Ikonen

Citations in the corpus

• Adipose tissue-derived factors: impact on health and disease. (2006, background): “Genetic deletion of caveolin-1 in the mouse results in adipocyte abnormalities including defects in lipolysis and thermogenesis (68, 69, 71).”
• CARNITINE TRANSPORT AND FATTY ACID OXIDATION (2016, unknown): “Similar features are seen in Cav1 knockout mice [44].”
• The multiple faces of caveolae (2007, background): “Cav1 −/− mice show decreased adiposity and are resistant to diet-induced obesit”
• The Human Obesity Gene Map: The 2005 Update (2006, background): “1 CAV1 Caveolin 1 Decreased adiposity; resistant to dietinduced obesity (321)”
• Caveolae: From Cell Biology to Animal Physiology (2002, methodology): “As mentioned before, Cav-1 expression is diminished by 2-fold in these lungs; however, the observed pathology cannot be due to this slight perturbation since Cav-1 heterozygous animals (who have a similar decrease in Cav-1 expression) fail to exhibit any lung pathology (Razani et al., 2002b).”
• Role of caveolae and caveolins in health and disease. (2004, background): “However, while the C-MAD-GFP fusion protein showed a predominant Golgi-like distribution, the N-MAD-GFP fusion protein localized to plasma membrane caveolae (145, 220).”