Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure.

Cristal M Hill,Liou Y Sun,Yimin Fang,Andrzej Bartke,Johanna G Miquet,Michal M Masternak

doi:10.1111/acel.12467

Abstract

SummaryGrowth hormone (GH) signaling stimulates the production of IGF‐1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high‐fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet‐induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD.

Highlights

According to the Center for Disease Control 2010 Adult Obesity report, the epidemic of obesity contributes to health disparities resulting in Accepted for publication 29 January 2016 higher medical attention and increased pharmaceutical needs and expenses in both middle-income and low-income populations in the United States (CDC, 2010)
At 12 weeks, during the final feeding phase, Ames dwarf mice fed high-fat diet (HFD) increased in body weight gain compared to control mice fed HFD (P < 0.0006), yet this seeming increase was not different compared to Ames dwarf mice fed standard diet (STD) (P = 0.07) (Fig. 1e)
These data suggest that growth hormone (GH)-deficient Ames dwarf mice respond to induction of obesity by HFD feeding greater than control mice fed the same diet

Summary

Introduction

According to the Center for Disease Control 2010 Adult Obesity report, the epidemic of obesity contributes to health disparities resulting in Accepted for publication 29 January 2016 higher medical attention and increased pharmaceutical needs and expenses in both middle-income and low-income populations in the United States (CDC, 2010). Individuals that are overweight or obese have greater risk of developing chronic diseases such as type 2 diabetes, cardiovascular disease (Kopelman, 2000), and cancer (Calle et al, 2003). These chronic diseases are strongly associated with older age and have negative impacts on longevity (Copaci et al, 2015; Sirbu et al, 2015). Mammalian survival depends on balanced nutrient consumption and the ability to fight infection, among other factors. Hormones such as growth hormone (GH) can function in both metabolic and immune roles. Longevity may be altered by metabolic stressors such as increased calorie consumption from diets high in fat

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