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Updated: Oct 22, 2025
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice
E Matthew Morris1,2, Roberto D Noland1, Michael E Ponte1
1Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Abstract:
The central integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previously, increased acute food intake following the chemical reduction of hepatic fatty acid oxidation and ATP levels was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a hepatocyte PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male, but not female, mice had a 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain compared to wildtype (WT) mice (p < 0.05). The greater weight gain was associated with altered feeding behavior and lower activity energy expenditure during the HFHS diet in LPGC1a males. WT and LPGC1a mice underwent sham surgery or HBV to assess whether vagal signaling was involved in the HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p < 0.05) in male WT mice, but not LPGC1a mice. These data demonstrate a sex-specific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need for a more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.
Insights
Reduced liver energy metabolism in male mice increases weight gain on high-fat/high-sucrose diets. Vagal signaling plays a role in diet-induced weight gain, but its involvement differs based on liver energy status.
Area of Science:
- Metabolic regulation
- Neuroendocrinology
- Energy homeostasis
Background:
- Systemic energy homeostasis relies on integrating peripheral neural signals.
- Previous studies suggested liver energy metabolism influences feeding behavior, but lacked specificity.
- Hepatic branch vagotomy (HBV) previously prevented food intake changes linked to liver metabolism alterations.
Purpose of the Study:
- To investigate the role of liver energy metabolism in systemic energy homeostasis using a mouse model.
- To assess the impact of reduced liver mitochondrial function on diet-induced weight gain.
- To determine the involvement of vagal signaling in diet-induced weight gain in the context of altered liver metabolism.
Main Methods:
- Utilized hepatocyte PGC1a heterozygous (LPGC1a) mice with reduced mitochondrial function.
- Administered a high-fat/high-sucrose (HFHS) diet to LPGC1a and wildtype (WT) mice.
- Performed sham surgery or hepatic branch vagotomy (HBV) on WT and LPGC1a mice.
- Monitored weight gain, feeding behavior, and activity energy expenditure.
Main Results:
- Male LPGC1a mice exhibited significantly greater HFHS diet-induced weight gain (70%) compared to WT males.
- This weight gain in male LPGC1a mice was linked to altered feeding behavior and reduced activity energy expenditure.
- HBV exacerbated HFHS-induced weight gain in WT males but did not affect LPGC1a males.
- These findings indicate a sex-specific effect of liver energy metabolism on diet-induced weight gain.
Conclusions:
- Reduced liver energy metabolism plays a sex-specific role in acute diet-induced weight gain.
- Vagal signaling's contribution to short-term diet-induced weight gain is complex and depends on liver metabolic status.
- Further research is needed for a nuanced understanding of vagal signaling in metabolic regulation.
