Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice

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.

Thermoneutral housing and preexisting obesity do not abolish the sexually dimorphic effects of olanzapine on weight gain in mice

“…To do so, male mice were housed in metabolic caging for 48 hours, with the first 24 hours serving as an acclimatization period. This initial period of familiarization is shorter than others have used [27, 28], but local animal ethic approval precluded us from housing mice for a longer duration. With this limitation in mind, energy expenditure/RER was measured over one full light and dark cycle.…”

Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus

“…Homeothermic animals oxidize lipids in BAT to maintain body temperature during winter, and thermogenic genes expressed in BAT can be upregulated after cold exposure ( Cannon and Nedergaard 2004 ; Watanabe et al 2008 ; Yamamoto et al 2011 ). Genes such as Ucp1 , Pgc1a , Tfam , and Prdm16 participate in mitochondrial oxidation and thermogenesis in BAT ( Seale et al 2007 ; Watanabe et al 2008 ; Vernochet et al 2012 ; Morris et al 2021 ). In our study, cold acclimation led to the upregulation of Ucp1 and Pgc1a in both RT and RN.…”