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Adiposity, Leptin Resistance, Hyperphagia, Hyperglycemia, Glucose Intolerance And Insulin Resistance In C57BL/6J Mice Fed

Male C57BLA5J mice approximately 6 wk old were housed 5 mice/cage, and were assigned to one of five diets, provided ad ttbitum: Dl2451 (45kcal%fat, lard, Research Diets, Inc., New Brunswick NJ), D12450B (10kcal%fat, lard control), D12330 (58kcal%fat, hydrogenated coconut ouVHCO), D12328 (llkcal%fat, HCO control), and Teklad8604 (12kcal%fat, soy). The D12451 mice had increased mean body weight vs. the D12450B group as early as 1 wk after initiation of diet, but D12451 average body weight was similar to mice fed 8604 diet. Mice fed D12451 decreased g/d intake, and maintained kcal intake similar to D12450B, D12328 or 8604 diets for 9 wk (12-13 kcal/d). Mice on D12330 diet ate progressively more each wk for 9 wk on diet, at which time they were eating approx 27 kcal/d. The D12451 mice developed insulin resistance, 3 h fasting and fed hyperglycemia, glucose intolerance, hyperinsulinemia, hyperleptinemia after 5-7 wk on diet.

Mice on D12330 gained weight more rapidly, were not insulin resistant or glucose intolerant at 5 wk on diet but were insulin resistant after 10 wk on diet. Mice maintained on high fat diets have greater abdominal and subcutaneous fat mass etermined by M RI than mice on low fat diet, even in the absence of a difference in total body weight. Mice (n=10/diet) were individually housed after 10 wk on diet, and acclimated for 1 wk. Individual housing increased food intake with all diets.

Leptin (10 mg/kg, i.p.) vs. vehicle (10 ml/kg, ip) was administered at the start of dark cycle daily for 3 d, and food intake monitored over 0-3,0-6 and 0-24h. Except for mice fed D12330 diet, all groups treated with leptin had significantly decreased food intake relative to vehicle in the 0-3h interval. In summary, both high fat diets produced obesity. D12451 produced insulin resistance with moderate obesity, while D12330 produced greater obesity first without insulin resistance, followed by later development of insulin and leptin

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Adiposity, Leptin Resistance, Hyperphagia, Hyperglycemia, Glucose Intolerance And Insulin Resistance In C57BL/6J Mice Fed (32 pages pdf file, 321 KB)