当前位置： SCI文献检索 > BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS期刊下所有文献 > A high fat diet-induced impaired glucose metabolism in mice with targeted deletion of calpain in osteoblasts.

A high fat diet-induced impaired glucose metabolism in mice with targeted deletion of calpain in osteoblasts.

Abstract：

:The ubiquitously expressed Calpains 1 and 2 belong to a family of calcium-dependent intracellular cysteine proteases. Both calpains are heterodimers consisting of a large subunit and a small regulatory subunit encoded by the gene Capns1. To investigate a role for the calpain small subunit in cells of the osteoblast lineage in vivo, we previously generated osteoblast-specific Capns1 knockout mice and characterized their bone phenotype. In this study, we further examined effects of low calcium and high fat diets on their bone, fat, and glucose homeostasis. Osteoblast-specific Capns1 knockout mice showed significantly reduced serum levels of total and uncarboxylated osteocalcin, and this was presumably due to their impaired bone formation and bone resorption. The reduced bone resorptive function of the mutant mice was also significant under a low calcium diet. Thus, these results suggest that reduced uncarboxylated osteocalcin levels of mutant mice were, at least in part, due to their osteoporotic bone with impaired bone resorptive function. Interestingly, unlike osteocalcin knockout mice, mutant mice on a normal chow diet were leaner than control littermates; this was likely due to their reduced food intake and overall lower energy homeostasis. To test this hypothesis, we next provided mutant mice with a high fat diet and further examined an effect of their reduced uncarboxylated osteocalcin levels on body composition and glucose metabolism. The average mean body weight of mutant mice became indistinguishable with that of controls after 2 weeks on a high fat diet, and continued to show an upward trend, at least, up to 6weeks. Moreover, mutant mice on a high fat diet exhibited a significant increase in serum levels of leptin and resistin, adipocyte-specific adipokines, and developed impaired glucose tolerance. Collectively, mice with osteoporosis and reduced bone resorptive function showed reduced serum uncarboxylated osteocalcin levels and were susceptible to increase body adiposity and develop impaired glucose tolerance under a high fat diet.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kashiwagi A,Fein MJ,Shimada M

doi

10.1016/j.bbrc.2011.04.134

subject

Has Abstract

pub_date

2011-06-03 00:00:00

pages

235-40

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(11)00741-8

journal_volume

409

pub_type

杂志文章

在线工具

A high fat diet-induced impaired glucose metabolism in mice with targeted deletion of calpain in osteoblasts.