Jasmine Encarnacion, Danielle M Smith, Joseph Choi, Joseph Scafidi, Michael J Wolfgang
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引用次数: 0
Abstract
The liver plays essential roles in maintaining systemic glucolipid homeostasis under ever changing metabolic stressors. Metabolic dysregulation can lead to both adaptive and maladaptive changes that impact systemic physiology. Here we examined disparate genetic and environmental metabolic stressors and identified Apolipoprotein A4 (ApoA4) as a circulating protein upregulated in liver-specific knockouts for Carnitine Palmitoyltransferase 2 and Pyruvate Carboxylase. We found this upregulation to be exacerbated by fasting and high fat or ketogenic diets. Unique among these models was a concomitant increase in Activating Transcription Factor 3 (Atf3). Liver-specific overexpression of Atf3 resulted in increased ApoA4 expression in a sex-dependent manner. To understand the requirement of Atf3 to metabolic stress, we generated liver-specific Atf3, Cpt2 double knockout mice. These experiments demonstrated the requirement for Atf3 in the induction of ApoA4 mRNA, ApoA4 protein, and serum triglycerides that were also sex dependent. These experiments reveal the roles of hepatic Atf3 and ApoA4 in response to metabolic stress in vivo.
期刊介绍:
The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.