Improved glucose and lipid metabolism in genetically obese mice lacking aP2

Citation
Kt. Uysal et al., Improved glucose and lipid metabolism in genetically obese mice lacking aP2, ENDOCRINOL, 141(9), 2000, pp. 3388-3396
Citations number
41
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
ENDOCRINOLOGY
ISSN journal
00137227 → ACNP
Volume
141
Issue
9
Year of publication
2000
Pages
3388 - 3396
Database
ISI
SICI code
0013-7227(200009)141:9<3388:IGALMI>2.0.ZU;2-N
Abstract
Adipocyte fatty acid-binding protein, aP2, is a member of the intracellular fatty acid binding protein family. Previously, studies have shown increase d insulin sensitivity in aP2-deficient mice with dietary obesity. Here, we asked whether aP2-related alterations in lipolytic response and insulin pro duction are features of obesity-induced insulin resistance and investigated the effects of aP2-deficiency on glucose homeostasis and lipid metabolism in ob/ob mice, a model of extreme obesity. ob/ob mice homozygous for the aP 2 null allele (ob/ ob-aP2(-/-)) became more obese than ob/ob mice as indica ted by significantly increased body weight and fat pad size but unaltered b ody length. However, despite their extreme adiposity, ob/ob-aP2(-/-) animal s were more insulin-sensitive compared with ob/ob controls, as demonstrated by significantly lower plasma glucose and insulin levels and better perfor mance in both insulin and glucose tolerance tests. These animals also showe d improvements in dyslipidemia and had lower plasma triglyceride and choles terol levels. Lipolytic response to beta-adrenergic stimulation and lipolys is-associated insulin secretion was significantly reduced in ob/ob-aP2(-/-) mice. Interestingly, glucose-stimulated insulin secretion, while virtually abolished in ob/ob controls, was significantly improved in ob/ob-aP2(-/-) animals. There were no apparent morphological differences in the structure or size of the pancreatic islets between genotypes. Taken together, the dat a indicate that in obesity, aP2-deficiency not only improves peripheral ins ulin resistance but also preserves pancreatic beta cell function and has be neficial effects on Lipid metabolism.