Hyperinsulinemia and ectopic fat deposition can develop in the face of hyperadiponectinemia in young obese rats.
Serum adiponectin has been reported to inversely correlate with the degree of adiposity in children. However, the relative contribution of adiponectin-dependent signaling to the development of metabolic syndrome in childhood obesity is unclear. We overfed prepubertal, male Sprague-Dawley rats a high-fat diet via total enteral nutrition. Excessive caloric intake led to obesity, increased body weight and fat mass; dyslipidemia; ectopic fat deposition; and hyperinsulinemia (P<.05). Expression of fatty acid transporter FAT/CD36 was elevated in both liver and skeletal muscle (P<.05). Hepatic Akt phosphorylation was elevated (P<.05) and FoxO1 protein in hepatic nuclear extracts was reduced (P<.05) in the face of hyperinsulinemia, whereas no increase in Akt phosphorylation or decrease in nuclear FoxO1 was observed in skeletal muscle. Overfeeding increased serum adiponectin concentration from 24.6±1.9 μg/ml to 46.3±5.9 μg/ml (P<.004), and positively correlated with increased adipose tissue mass. The expression of the inflammatory cytokine tumor necrosis factor α in the adipose tissue was unchanged. Adiponectin-mediated adenosine monophosphate (AMP) kinase phosphorylation, peroxisome proliferator-activator receptor-α expression and the expression of genes involved in fatty acid oxidation were elevated in both liver and muscle (P<.05). These data (1) demonstrate that excessive intake of a high-fat diet in young rats results in "adiponectin-independent" increases in ectopic fat deposition and hyperinsulinemia, (2) suggest that fatty acid transport is a major mechanism underlying ectopic fat deposition, (3) demonstrate tissue-specific differences in the response of Akt-FoxO signaling to hyperinsulinemia following the development of pediatric obesity and (4) suggest age-related differences in the role of adiponectin in pathological responses associated with obesity.
Marecki
John C
JC
Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA.
Ronis
Martin J J
MJ
Shankar
Kartik
K
Badger
Thomas M
TM
D052242:Adiponectin / Q000097:blood*; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity; D000367:Age Factors; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D004750:Enteral Nutrition; D005234:Fatty Liver / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000378:metabolism*; D044343:Overnutrition / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain
D052242:Adiponectin; D018955:CD36 Antigens