Abstract
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin secreted from enteroendocine K cells after nutrient ingestion. Fat strongly induces GIP secretion, and GIP hypersecretion is involved in high-fat diet-induced obesity and insulin resistance. Aging also induces GIP hypersecretion, but its effect on body weight gain and insulin sensitivity remains unclear. In the present study, we investigated the effect of GIP on age-related body weight gain and insulin resistance using GIP-knockout homozygous (GIP−/−) and heterozygous (GIP+/−) mice, which have entirely absent and 50% reduced GIP secretion compared to wild-type (WT) mice, respectively. Under 12% fat-containing normal diet feeding condition, body weight was significantly lower in GIP−/− mice compared to that in WT and GIP+/− mice from 38 weeks of age, while there was no significant difference between WT and GIP+/− mice. Visceral and s.c. fat mass were also significantly lower in GIP−/− mice compared to those in WT and GIP+/− mice. During oral glucose tolerance test, blood glucose levels did not differ among the three groups. Insulin levels were significantly lower in GIP−/− mice than those in WT and GIP+/− mice. During insulin tolerance test, GIP−/− mice showed higher insulin sensitivity than that of WT and GIP+/− mice. Adiponectin mRNA levels were increased and leptin mRNA levels tended to be decreased in adipose tissue of GIP−/− mice. These results demonstrate that GIP is involved in age-related obesity and insulin resistance and that inhibition of GIP secretion alleviates age-related fat mass gain and insulin resistance under carbohydrate-based diet feeding condition.
Highlights
Life expectancy has increased in developed countries and is accompanied by the main age-related changes in body composition, which are an increase in fat mass and a decrease in muscle mass
We previously investigated the effects of absent and 50% reduced Glucose-dependent insulinotropic polypeptide (GIP) secretion on high-fat diet (HFD)-induced obesity and insulin resistance using GIP-knockout mice; we found that reduced GIP secretion as well as absent GIP secretion alleviates fat mass gain and insulin resistance under HFD feeding condition (Nasteska et al 2014)
These results demonstrate that reduced GIP secretion as well as absent GIP secretion contribute to alleviation of HFD-induced obesity and insulin resistance
Summary
Life expectancy has increased in developed countries and is accompanied by the main age-related changes in body composition, which are an increase in fat mass and a decrease in muscle mass. Visceral fat accumulation causes insulin resistance through inflammation (Kalyani et al 2014) This age-related change is called ‘sarcopenic obesity’, and is an important health issue in aging societies (Prado et al 2012, Cleasy et al 2016). Obesity is related to a decline of activities of daily living (ADL) in elderly people and is related to the high prevalence of medical disorders such as diabetes, hyperlipidemia, and hypertension (Cheng et al 2013, Chang et al 2017). It is important for elderly people to prevent excessive fat accumulation with aging.
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