The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity
FASEB JOURNAL, vol.21, no.13, pp.3629-3639, 2007 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 21 Issue: 13
- Publication Date: 2007
- Doi Number: 10.1096/fj.07-8290com
- Journal Name: FASEB JOURNAL
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.3629-3639
- Istanbul University Affiliated: Yes
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-PGC1 alpha axis, a well-established 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.