Resistance to high-fat diet-induced obesity but exacerbated insulin resistance in mice overexpressing preadipocyte factor-1 (Pref-1): a new model of partial lipodystrophy.
OBJECTIVE
White adipose tissue is a critical regulator of whole-body glucose metabolism. Preadipocyte factor-1 (Pref-1) is a secreted protein that inhibits adipocyte differentiation, both in vitro and in vivo. In this study, we have investigated the effects of Pref-1 overexpression on whole-body glucose homeostasis and its contribution to the development of insulin resistance.


METHODS
To gain insight into the role of Pref-1 on the onset of insulin resistance and type 2 diabetes, we measured body composition and whole-body insulin-stimulated glucose metabolism during a hyperinsulinemic-euglycemic clamp in Pref-1 transgenic and wild-type control mice fed a high-fat diet.


RESULTS
Mice overexpressing Pref-1 were resistant to high-fat diet-induced obesity, as reflected by a marked reduction in adipose tissue mass. However, Pref-1-overexpressing mice were severely insulin resistant, mainly because of a reduction in insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. The aggravated insulin resistance was associated with impaired insulin signaling and increased diacylglycerol content in skeletal muscle.


CONCLUSIONS
Mice overexpressing Pref-1 are insulin resistant despite being protected from diet-induced obesity and may provide a new rodent model for the study of lipodystrophic disorders.
Villena
Josep A
JA
Department of Nutritional Science and Toxicology, University of California, Berkeley, CA, USA.
Choi
Cheol Soo
CS
Wang
Yuhui
Y
Kim
Sheene
S
Hwang
Yu-Jin
YJ
Kim
Young-Bum
YB
Cline
Gary
G
Shulman
Gerald I
GI
Sul
Hei Sook
HS
D052242:Adiponectin / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D002135:Calcium-Binding Proteins; D004041:Dietary Fats / Q000378:metabolism*; D004195:Disease Models, Animal; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D020738:Leptin / Q000502:physiology; D052496:Lipodystrophy, Familial Partial / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D052242:Adiponectin; D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D004041:Dietary Fats; C512925:Dlk1 protein, mouse; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011993:Recombinant Fusion Proteins