Petite Integration Factor 1 (PIF1) helicase deficiency increases weight gain in Western diet-fed female mice without increased inflammatory markers or decreased glucose clearance
| Autor: | Robert M. O'Doherty, Nikita Desai, Yanxia Chu, Michael J. Jurczak, Frances Belmonte, Nikolaos Dedousis, Yingze Zhang, Sylvie Bannwarth, Ian Sipula, Brett A. Kaufman, Véronique Paquis-Flucklinger, Lea Harrington, Aatur D. Singhi |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
medicine.medical_specialty Wild type Adipose tissue 030209 endocrinology & metabolism Inflammation Metabolism Biology medicine.disease 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Gene expression medicine Glucose homeostasis medicine.symptom Steatosis Weight gain 030304 developmental biology |
| Popis: | 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 removal 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 were protected against 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 gene expression of inflammatory markers 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. |
| Databáze: | OpenAIRE |
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