Petite Integration Factor 1 (PIF1) helicase deficiency increases weight gain in Western diet-fed female mice without increased inflammatory markers or decreased glucose clearance

PLoS One. 2019 May 28;14(5):e0203101. doi: 10.1371/journal.pone.0203101. eCollection 2019.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Body Composition
  • Cholesterol / metabolism
  • Cytokines / metabolism
  • DNA Helicases / deficiency*
  • Diet, Western*
  • Energy Metabolism
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Female
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Inflammation Mediators / metabolism*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism
  • Motor Activity
  • Weight Gain / genetics*


  • Cytokines
  • Inflammation Mediators
  • Cholesterol
  • DNA Helicases
  • Pif1 protein, mouse
  • Glucose