Changes in adiponectin and inflammatory genes in response to hormonal imbalances in female mice and exacerbation of depot selective visceral adiposity by high-fat diet: implications for insulin resistance.
Early obesity and late onset of insulin resistance associated with hormonal imbalances occur in FSH receptor-deficient follitropin receptor knockout female mice. This study tests the hypothesis that chronic high-fat diet aggravates obesogenic changes in a depot-specific manner and explores some molecular links of hormone imbalances with insulin resistance. In SV 129 mice, hormonal imbalances seem obligatory for exacerbation of diet-induced obesity. Visceral adiposity, glucose intolerance, and lipid disturbances in 9-month follitropin receptor knockout females were associated with decrease in adiponectin signaling. High-molecular-weight plasma adiponectin and adipose tissue adiponectin mRNA were decreased. Adiponectin receptors R1 and R2 mRNA was selectively altered in mesenteric fat but not periuterine fat. R2 decreased in the liver and R1 was higher in muscle. Whereas hepatic adenosine monophosphate T-activated protein kinase activity was down-regulated, both phosphoenolpyruvate carboxykinase and glucose-6-phosphatase enzymes were up-regulated. Longitudinally, diminishing sex hormone signaling in adipose tissue was associated with progressive down-regulation of adiponectin activity and gradual impaired glucose tolerance. Chronic high-fat diet in SV129 wild-type mice did not produce overt obesity but induced visceral fat depot changes accompanied by liver lipid accumulation, high cholesterol, and up-regulation of inflammation gene mRNAs. Thus, TNF-alpha, C-C motif chemokine receptor-2, and C-C motif chemokine ligand-2 were selectively elevated in mesenteric fat without altering glucose tolerance and adiponectin signaling. Our study highlights adiponectin signaling and regulation to be involved in hormone imbalance-induced insulin resistance and demonstrates selective visceral adipose depot alterations by chronic high-fat diet and induction of inflammatory genes.
Zhang
Hui
H
Molecular Reproduction Research Laboratory, Clinical Research Institute of Montréal, 110 Pine Avenue West, Montréal, Québec, Canada.
Chen
Xinlei
X
Aravindakshan
Jayaprakash
J
Sairam
M Ram
MR
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D015151:Immunoblotting; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008954:Models, Biological; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D052242:Adiponectin; D004041:Dietary Fats; D054419:Receptors, Adiponectin; D011962:Receptors, FSH; D005947:Glucose