Downregulation of adiponectin/AdipoR2 is associated with steatohepatitis in obese mice.
BACKGROUND
Recent evidence suggests that obesity is associated with hypo-adiponectinmia and chronic inflammation. Adiponectin regulates fat storage, energy expenditure, and inflammation. We propose that high fat diet induces steatohepatitis, reduces serum adiponectin, and liver adiponectin receptors.


METHODS
A 4-week-old C57BL male mice were fed high fat diet (n = 8) or regular chow (control; n = 6) for 7 weeks. Body weight, liver weight, and serum adiponectin were measured. Liver sections were stained with hematoxylin and eosin and oil red for fat content. Liver homogenates were used for protein (immunoblotting) and mRNA (reverse transcription PCR) of Toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, sterol regulatory element-binding proteins (SREBP)-1c, and adiponectin receptors (AdipoR1/AdipoR2) in addition to nuclear phorsphorylated p65NF-kappaB. Gels were quantified using densitometry; t test was used, and p < 0.05 was significant.


RESULTS
High fat diet increased body (50%) and liver weight (33%), as well as hepatocyte fat content and ballooning. Mice fed high fat diet exhibited reduced serum adiponectin and liver AdipoR2. High fat diet increased hepatic levels of SREBP-1c, TLR4, TNF-alpha, and IL-6 protein and mRNA and increased activation of p65NF-kappaB.


CONCLUSIONS
Diet-induced liver steatosis is associated with increased lipogensis, upregulation of pro-inflammatory cytokines, and transcription factors as well as downregulation of AdipoR2. Reduction in serum adiponectin suggests that adiponectin signaling may be the crosslink between high fat diet, hepatic inflammation, and nonalcoholic fatty liver disease.
Peng
Yanhua
Y
Department of Surgery, University of South Florida, Tampa, FL, USA.
Rideout
Drew
D
Rakita
Steven
S
Sajan
Mini
M
Farese
Robert
R
You
Min
M
Murr
Michel M
MM
D052242:Adiponectin / Q000097:blood / Q000502:physiology*; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D015536:Down-Regulation / Q000502:physiology*; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D054419:Receptors, Adiponectin / Q000097:blood / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
D052242:Adiponectin; D004041:Dietary Fats; D054419:Receptors, Adiponectin; D051780:Sterol Regulatory Element Binding Protein 1; C475421:adiponectin receptor 2, mouse