Peripheral Leptin Administration and Food Intake Measurement
behavioralmouseC57BL/6 and AKR
Objective: Determine whether diet-induced obesity in mice produces resistance to peripheral and/or central leptin treatment by measuring food intake responses to leptin administration over time
Materials & Equipment Checklist
7 items
Gather these items before starting the experiment. Check off items as you prepare.
Equipment3
Not specified • Not specified • Not specified • Not specified
As an Amazon Associate, we earn from qualifying purchases. Product links help support this free resource.
Protocol Steps
View Abstract
Leptin administration reduces obesity in leptin-deficient ob/ob mice; its effects in obese humans, who have high circulating leptin levels, remain to be determined. This longitudinal study was designed to determine whether diet-induced obesity in mice produces resistance to peripheral and/or central leptin treatment. Obesity was induced in two strains of mice by exposure to a 45% fat diet. Serum leptin increased in proportion to body weight (P < 0.00001). 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; mice on 10% fat diet retained leptin sensitivity. 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. 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. These data demonstrate that, in a diet-induced obesity model, mice exhibit resistance to peripherally administered leptin, while retaining sensitivity to centrally administered leptin.
1
Induce obesity through high fat diet exposure
Expose two strains of mice (C57BL/6 and AKR) to a 45% fat diet to induce obesity
Not specifiedNot specified
Note: Two dietary conditions were used: 45% fat diet and 10% fat diet control
View evidence from paper
“Obesity was induced in two strains of mice by exposure to a 45% fat diet”
2
Measure baseline serum leptin levels
Collect serum and measure leptin levels in relation to body weight
Not specifiedNot specified
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)”
3
Administer peripheral leptin to C57BL/6 mice
Administer leptin peripherally to C57BL/6 mice on high fat diet and measure food intake response
16 days of dietary treatmentNot specified
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”
4
Administer peripheral leptin to C57BL/6 mice on low fat diet
Administer leptin peripherally to C57BL/6 mice on 10% fat diet as control
Not specifiedNot specified
Note: Mice on low fat diet retained leptin sensitivity
View evidence from paper
“mice on 10% fat diet retained leptin sensitivity”
5
Administer peripheral leptin to AKR mice
Administer leptin peripherally to AKR mice on both 10% and 45% fat diets and measure food intake response
16 days and 56 days of dietary treatmentNot specified
Note: AKR mice showed initial response at 16 days but developed resistance by 56 days on both diets
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”
6
Administer central leptin via intracerebroventricular infusion
Administer leptin centrally via single intracerebroventricular infusion to peripherally leptin-resistant AKR mice on 45% fat diet
Single infusionNot specified
Note: Central leptin administration produced 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”
7
Measure food intake and body weight changes
Monitor and record food intake and body weight changes in response to leptin administration
Throughout experimental periodNot specified
Note: Food intake and body weight were primary outcome measures
View evidence from paper
“with a dose-dependent decrease in food intake (P < 0.00001) and body weight (P < 0.0001)”
Subjects / Specimens
Species
mouse
Strain
C57BL/6 and AKR
Age
Not specified
Sex
unknown
Weight
Not specified
Two strains of mice were used in this longitudinal study