Abstract
Obesity is one of the major health problems of our times. Elucidating the signaling mechanisms by which high-fat caloric diet induces obesity is critical for the understanding of this condition and for the development of therapeutic strategies for its treatment. Here, we demonstrate a novel role for protein CD38 as a regulator of body weight during a high-fat diet. CD38 is a ubiquitous enzyme that catalyzes the synthesis of second messengers and has been implicated in the regulation of a wide variety of signaling pathways. We report that CD38-deficient mice are protected against high-fat diet-induced obesity owing to enhanced energy expenditure. In fact, calorimetric studies indicate that CD38-deficient animals have a higher metabolic rate compared to control mice. Analysis of the mechanism revealed that this resistance to diet-induced obesity is mediated at least in part via a NAD-dependent activation of SIRT-PGC1α axis, a wellestablished cascade, involved in the regulation of mitochondrial biogenesis and energy homeostasis. Thus, together these results identify a novel pathway regulating body weight and clearly show that CD38 is a nearly obligatory component of the cellular cascade that led to diet-induced obesity.
Original language | English (US) |
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Pages (from-to) | 3629-3639 |
Number of pages | 11 |
Journal | FASEB Journal |
Volume | 21 |
Issue number | 13 |
DOIs | |
State | Published - Nov 2007 |
Keywords
- Knockout mice
- Liver
- Nicotinamide adenine dinucleotide
- PGC1α
- SIRT1
- Sirtuins
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics