Diet-induced Obesity Model
Objective: To determine whether diet-induced obesity in mice produces resistance to peripheral and/or central leptin treatment, and to measure serum leptin levels in proportion to body weight
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Equipment1
Not specified • Not specified • Not specified • Not specified
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Protocol Steps
Induce obesity with high fat diet
Expose two strains of mice (C57BL/6 and AKR) to a 45% fat diet to induce obesity
Note: This is a longitudinal study design
View evidence from paper
“Obesity was induced in two strains of mice by exposure to a 45% fat diet.”
Measure serum leptin levels
Collect serum and measure leptin levels in relation to body weight changes
Note: Serum leptin increased in proportion to body weight with statistical significance
View evidence from paper
“Serum leptin increased in proportion to body weight (P < 0.00001).”
Test peripheral leptin sensitivity in C57BL/6 mice
Administer leptin peripherally to C57BL/6 mice on 45% fat diet and measure food intake response
Note: Initial response observed, but leptin resistance developed after 16 days on high fat diet
View evidence from paper
“Whereas C57BL/6 mice initially responded to peripherally administered leptin with a marked decrease in food intake, leptin resistance developed after 16 d on high fat diet”
Test peripheral leptin sensitivity in AKR mice
Administer leptin peripherally to AKR mice on both 10% and 45% fat diets and measure food intake response
Note: AKR mice showed initial sensitivity at 16 days but developed resistance by 56 days on both diet types
View evidence from paper
“In AKR mice, peripheral leptin significantly decreased food intake in both 10 and 45% fat-fed mice after 16 d of dietary treatment. However, after 56 d, both groups became resistant to peripherally administered leptin.”
Test central leptin administration
Administer leptin centrally via intracerebroventricular infusion to peripherally leptin-resistant AKR mice on 45% fat diet
Note: Central leptin administration produced robust dose-dependent responses in food intake and body weight
View evidence from paper
“Central administration of leptin to peripherally leptin-resistant AKR mice on 45% fat diet resulted in a robust response to leptin, with a dose-dependent decrease in food intake (P < 0.00001) and body weight (P < 0.0001) after a single intracerebroventricular infusion.”