Impact of reduced insulin‐like growth factor‐1/insulin signaling on aging in mammals: novel findings

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

“…3b) ( P  = 0.30). Previous reports have shown that Ames dwarf mice are more insulin sensitive compared to control mice when they are fed STD (Bartke, 2008; and Bartke et al ., 2011). As expected, Ames dwarf mice fed STD were more insulin sensitive compared to control mice fed STD as shown by area under the curve ( P  < 0.004) (Fig.…”

“…To further clarify endocrine function, we evaluated IGF‐1 levels in Ames dwarf and control mice fed either diets. Ames dwarf mice fed STD typically have undetectable levels of IGF‐1 (Bartke, 2008). We observed the expected decrease of systemic IGF‐1 levels in Ames dwarf compared to control mice ( P  < 0.0001) and there was no difference IGF‐1 levels in Ames dwarf or control mice fed HFD compared to their counterparts fed STD (Fig.…”

“…The removal of epididymal visceral fat decreased levels of adiponectin and reduced insulin sensitivity in GHR‐KO and Ames dwarf mice (Masternak et al ., 2012; Menon et al ., 2014). In the context that in the absence of GH signaling, visceral fat exerts unexpected beneficial influence on insulin sensitivity (Bartke, 2008), and in this study Ames dwarf mice are resistant to the detrimental effects of HFD, we were interested in determining whether transplantation of visceral fat from Ames dwarf mice fed HFD into control littermates fed the same diet could improve their insulin sensitivity. In this experiment, we fed Ames dwarf mice and control mice HFD for 12 weeks and accessed their insulin sensitivity by ITT.…”

“…Long‐lived hypopituitary Ames dwarf mice and GH‐resistant GHR‐KO mice share various metabolic characteristics such as suppressed levels of circulating IGF‐1, insulin, and glucose and are more insulin sensitive, yet have increased adiposity compared to their control littermates (Berryman et al ., 2004; Bartke, 2008; and Bartke et al ., 2011). The visceral adipose tissue in Ames dwarf and GHR‐KO mice has been reported to benefit their metabolic profile, which is related to their extended longevity.…”

“…Abnormal high levels of GH can contribute to the induction of insulin resistance (Weaver et al ., 1995), alter inflammatory cytokine levels (Uronen‐Hansson et. al ., 2003; Bartke, 2008), and can reduce life expectancy in both mice (Brown‐Borg et al ., 1996; Bartke et al ., 1998) and humans (Chertman et al ., 2000). Disruption of GH signaling by either reducing plasma GH levels or by GH receptor deletion significantly extends lifespan in mice as reported in Ames dwarf mice, Snell dwarf mice, GH receptor/GH‐binding protein gene knockout mice (GHR‐KO mice), and GH‐releasing hormone knockout mice (GHRH‐KO) (Brown‐Borg et al ., 1996; Coschigano et al ., 2000; Bartke et al ., 2011).…”