Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity

Abstract

Insulin resistance develops with ageing in humans and rodents. Here, we have studied the evolution of insulin sensitivity with ageing trying to discriminate the role of adiposity from that of ageing in this process. We performed oral glucose tolerance tests and determined overall and tissue-specific glucose utilization under euglycemic-hyperinsulinemic conditions in 3-, 8-, and 24-month-old rats fed ad libitum, and in 8-and 24-month-old rats after 3 months of calorie restriction. Body composition and adipocytederived cytokines such as leptin, resistin, and adiponectin were analyzed. Overall insulin sensitivity decreases with ageing. Calorie restriction improves global insulin sensitivity in 8-but not in 24-month-old rats. Insulin-stimulated glucose utilization in adipose tissues decreases in 8 months, while in oxidative muscles it reaches significance only in older rats. Calorie restriction restores adipose tissue insulin sensitivity only in 8-month-old rats and no changes are observed in muscles of 24-month-old rats. Resistin and leptin increase with ageing. Food restriction lowers resistin and increases adiponectin in 8-month-old rats and decreases leptin in both ages. Visceral and total fat increase with ageing and decrease after calorie restriction. We conclude that accretion of visceral fat plays a key role in the development of insulin resistance after sexual maturity, which is reversible by calorie restriction. With aging, accumulation of retroperitoneal and total body fat leads to impaired muscle glucose uptake and to a state of insulin resistance that is difficult to reverse.

Chronic caffeine intake reverses age-induced insulin resistance in the rat: effect on skeletal muscle Glut4 transporters and AMPK activity

“…Visceral fat mass was increased both in 12 M and 24 M animals, with a more pronounced effect in the 12 M group. Supporting our data, it has been observed that the decrease of insulin sensitivity until 8 months of age is paralleled by a significant increase in visceral and total fat mass, but between 8 and 24 months of age, insulin sensitivity decreases further without significant changes in percent visceral adiposity (Escrivá et al 2007). In our experimental setting, caffeine significantly decreased visceral fat mass in the 12 M, but not in the 24 M, group.…”

“…In our experimental setting, caffeine significantly decreased visceral fat mass in the 12 M, but not in the 24 M, group. Escrivá and coworkers also showed that in 24-month-old rats, the accumulation of retroperitoneal and total body fat is more significant than visceral fat buildup (Escrivá et al 2007). We may have missed a significant effect of caffeine on adipose tissue in 24 M rats, considering that we did not assess whole body fat.…”

Adipose tissue loss in adjuvant arthritis is associated with a decrease in lipogenesis, but not with an increase in lipolysis

“…The decrease in serum concentrations of adiponectin and its gene expression in WAT does not seem to be secondary to a decrease in food intake. On the contrary, dietary energy restriction leads to an increase in adiponectin secretion (Escrivá et al 2007, Martin et al 2007. The inhibitory effect of arthritis on adiponectin can be due to the inflammatory response, since macrophage-derived factors inhibit adipocyte differentiation as well as adiponectin and FAS gene expression in murine and human preadipocytes (Constant et al 2006).…”

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

“…The GH/IGF-I and insulin system are also significantly altered following fasting and DR. However, differences in GH response and also in the degree of reduction in circulating IGF-I, IGFBP-3, insulin and in the increase of IGFBP-1 and insulin-sensitivity are evitable (Bartke and Turyn 2001;Bonkowski et al, 2009;Breese et al, 1991;Buschemeyer et al, 2010;Dunn et al, 1997;Escriva et al, 2007;Frystyk et al, 1999;Heijboer et al, 2005;Lee et al, 2010;Shimokawa et al, 2003;Wang et al, 2006;Zhao et al, 2010). Corticosteroids tend to increase more following fasting compared with DR (Sabatino et al, 1991;Shen et al, 2009); body temperature showed a steeper decrease following fasting compared with DR (Koizumi et al, 1992;Longo and Finch 2003a;Shen et al, 2009).…”