title: Ubiquitin ligase Cbl-b and obesity-induced insulin resistance.
abstract: Obesity causes type 2 diabetes, atherosclerosis and cardiovascular diseases by inducing systemic insulin resistance. It is now recognized that obesity is related to chronic low-grade inflammation in adipose tissue. Specifically, activated immune cells infiltrate adipose tissue and cause inflammation. There is increasing evidence that activated macrophages accumulate in the hypertrophied adipose tissue of rodents and humans and induce systemic insulin resistance by secreting inflammatory cytokines. Accordingly, a better understanding of the molecular mechanisms underlying macrophage activation in adipose tissue will facilitate the development of new therapeutic strategies. Currently, little is known about the regulation of macrophage activation, although E3 ubiquitin ligase Casitas B-lineage lymphoma (Cbl)-b was identified recently as a novel negative regulator of macrophage activation in adipose tissue. Cbl-b, which is a suppressor of T- and B-cell activation, inhibits intracellular signal transduction by targeting some tyrosine kinases. Notably, preventing Cbl-b-mediated macrophage activation improves obesity-induced insulin resistance in mice. c-Cbl is another member of the Cbl family that is associated with insulin resistance in obesity. These reports suggest that Cbl-b and c-Cbl are potential therapeutic targets for treating obesity-induced insulin resistance. In this review, we focus on the importance of Cbl-b in macrophage activation in aging-induced and high-fat diet-induced obesity.
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Abe
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirasaka
authors.forename: Shohei
authors.initials: S
authors.lastname: Kohno
authors.forename: Arisa
authors.initials: A
authors.lastname: Ochi
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamagishi
authors.forename: Ayako
authors.initials: A
authors.lastname: Ohno
authors.forename: Shigetada
authors.initials: S
authors.lastname: Teshima-Kondo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000375:Aging / Q000502:physiology; D000818:Animals; D059305:Diet, High-Fat; D006801:Humans; D007107:Immune System / Q000201:enzymology / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008262:Macrophage Activation / Q000235:genetics; D051379:Mice; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl