Journal Article

Petite Integration Factor 1

Zhang, Yingze, Shiva, Sruti, Paquis-Flucklinger, Véronique, Harrington, Lea, Belmonte, Frances R, Sipula, Ian, Dedousis, Nikolaos, Chu, Yanxia, Kaufman, Brett A, Singhi, Aatur D, Desai, Nikita A, O'Doherty, Robert M, Bannwarth, Sylvie, Jurczak, Michael J

2019

Overview

Petite Integration Factor 1 (PIF1) is a multifunctional helicase present in nuclei and mitochondria. PIF1 knock out (KO) mice exhibit accelerated weight gain and decreased wheel running on a normal chow diet. In the current study, we investigated whether Pif1 ablation alters whole body metabolism in response to weight gain. PIF1 KO and wild type (WT) C57BL/6J mice were fed a Western diet (WD) rich in fat and carbohydrates before evaluation of their metabolic phenotype. Compared with weight gain-resistant WT female mice, WD-fed PIF1 KO females, but not males, showed accelerated adipose deposition, decreased locomotor activity, and reduced whole-body energy expenditure without increased dietary intake. Surprisingly, PIF1 KO females did not show obesity-induced alterations in fasting blood glucose and glucose clearance. WD-fed PIF1 KO females developed mild hepatic steatosis and associated changes in liver gene expression that were absent in weight-matched, WD-fed female controls, linking hepatic steatosis to Pif1 ablation rather than increased body weight. WD-fed PIF1 KO females also showed decreased expression of inflammation-associated genes in adipose tissue. Collectively, these data separated weight gain from inflammation and impaired glucose homeostasis. They also support a role for Pif1 in weight gain resistance and liver metabolic dysregulation during nutrient stress.

• Publisher: Public Library of Science
• Subject: Adipose tissue / Analysis / Blood glucose / Body weight / Care and treatment / Diet / EDTA / Fasting / Gene expression / Genes / Glucose / Health aspects / Homeostasis / House mouse / Inflammation / Obesity / Type 2 diabetes / Weight gain