title: Hyperinsulinemia and ectopic fat deposition can develop in the face of hyperadiponectinemia in young obese rats.
abstract: 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.
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Marecki
authors.forename: Martin J J
authors.initials: MJ
authors.lastname: Ronis
authors.forename: Kartik
authors.initials: K
authors.lastname: Shankar
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
mesh_terms: 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
chemical_list: D052242:Adiponectin; D018955:CD36 Antigens