Effect of dehydroepiandrosterone on protein and fat digestibility, body protein and muscular composition in high-fat-diet-fed old rats

Abstract

The main objective of the present study was to examine the effects of dehydroepiandrosterone (DHEA) on the digestive efficiency of dietary protein and fat. Second, we analysed the specific changes in muscle composition induced by the hormone. DHEA was given in the diet (0·5 %, w/w) to 75-week-old, high-fat-fed Sprague -Dawley rats (n 11) for 13 weeks; age-and weight-matched rats fed on the same diet without DHEA supplementation were used as controls (n 10). To determine dietary protein and fat apparent digestibility coefficients, 1-week 24 h faecal depositions were collected. In parallel, urine N was assessed. These assays were performed twice, in the short term (2-week treatment) and in the long term (13-week treatment). Body and gastrocnemius muscle compositions were also analysed. The present results show that DHEA decreased energy intake, body weight, body fat, adipocyte size and number (P,0·001). The feed efficiency ratio indicates that DHEA-treated rats were less efficient in transforming nutrients fed into their own biomass. Also, a short-term reduction in protein digestibility (P, 0·05) and in body-protein degradation (P, 0·01) was found in DHEA-treated rats, resulting in an increased content of body protein (P,0·05). Gastrocnemius muscles were smaller, as a result of fat (P, 0·05) but not protein reduction. In conclusion, we confirm the slimming effect of DHEA and, for the first time, we demonstrate that DHEA has an effect at the digestive level. The anti-obesity properties of DHEA could be related to a reduction in protein digestibility in the short term and a protective effect on body protein with a selective mass loss from body fat.Dehydroepiandrosterone: Digestibility: Body protein: Gastrocnemius muscle: Obesity: High-fat diets Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are the most abundant circulating steroids in man and the precursors for most steroid hormones (Orentreich et al. 1984). Serum concentrations of DHEA and DHEA-S are age dependent; in man, they rapidly increase at puberty, reach their peak levels between 20 and 30 years of age, and then decrease gradually (Yamaji & Ibayashi, 1969;Orentreich et al. 1984;Vermeulen, 1995;Macario et al. 1999). This evolution, coincident with the incipient loss of physical performance, has led these hormones to be known as 'the hormones of youth ' (Nawata et al. 2002).Far from being just biochemical intermediates, these steroids per se have been reported to have positive effects in the prevention and treatment of certain pathologies, especially the age-related ones, such as cancer (Schwartz et al. 1988;Ratko et al. 1991;Kawai et al. 1995), CVD (Ebeling & Koivisto, 1994), cognitive deterioration (Yanase et al. 1996), insulin resistance and obesity (Williams et al. 1993).In man, the action of DHEA on obesity is not generally agreed. Some studies report no relationship between plasma levels of these steroids and body weight and fat (Azziz et al. 1991;Phillips, 1993;Barret-Connor & Ferrara, 1996;Macario et al. 1999), while others find a negative co...

Dehydroepiandrosterone modifies rat fatty acid composition of serum and different adipose tissue depots and lowers serum insulin levels

“…We had previously reported that DHEA administration to our rats led to significant reductions in food intake, body weight, total body fat content, the weight of different adipose depots, and adipocyte size (de Heredia et al 2007). In addition, we found that DHEA-treated rats had significantly lower serum insulin concentrations and a tendency to lower HOMA-IR index (Sánchez et al 2008).…”

“…Besides, low serum concentrations of these hormones, they have been associated with certain pathological states that increase their prevalence during ageing. Among the beneficial effects of DHEA, we can find cancer prevention (Ratko et al 1991, Kawai et al 1995, amelioration of cognitive function (Yanase et al 1996), or protection against cardiovascular disease (Ebeling & Koivisto 1994), atherosclerosis (Nestler et al 1992), or obesity (Richards et al 2000, Abadie et al 2001, de Heredia et al 2007. Improvement of peripheral insulin sensitivity has also emerged as one of DHEA's relevant actions; indeed, we and other authors have previously observed that DHEA administration to rodents reduced significantly serum insulin concentrations (Richards et al 2000, Abadie et al 2001, Sánchez et al 2008.…”

Dehydroepiandrosterone prevents age-associated alterations, increasing insulin sensitivity

“…At the age of 7 weeks rats were fed with a HF diet. The diet contained (expressed as a percentage of dry mass) 18.4% protein, 50.4% carbohydrates (50% of which was sucrose) and 19.6% fat; the energy content was 1880 kJ/100 g, and fat amounted for 39% total dietary energy [29]. Palm oil was used as source of fat, and fatty acid composition of the diet was 53.6% saturated fatty acids, 36.3% monounsaturated fatty acids, 9.5% polyunsaturated fatty acids and 0.6% trans fatty acids.…”

“…DHEA administration has long been associated with reduced weight gain in growing animals and with weight loss in mature animals [23][24][25][26][27][28]. DHEA may reduce weight gain by inhibiting food intake [23,29] or may cause a metabolic effect, as evidenced by less weight gain despite no change in food intake [25,30]. In addition, DHEA treatment has antidiabetic effects in some strains of mice [20] and reduces serum insulin levels in hyperinsulinemic, diet-induced or genetically obese rats [25,27].…”

Effects of Dehydroepiandrosterone on Gross Morphology and Behavior of Perimenopausal Rats

“…The decrease in body weight gain may be related to the decrease in food intake (Weindruch et al, 1984), or related to the decrease the abdominal or body fats (Cleary and Zisk, 1986;Villareal and Holloszy, 2004;Ma et al, 2008). However, other studies reported that DHEA treatment causes a decrease in the body weight (Tagliaferro et al, 1986;Mohan et al, 1990;Yamada et al, 1991;Han et al, 1998;Ng et al, 1999;Richards et al, 2000;Kopplow et al, 2005;de Heredia et al, 2007;Caldwell et al, 2014;Chen et al, 2015), and other studies found no effect for DHEA on body weight (Lea-Currie et al, 1997 a, b;Aragno et al, 2004;Sander et al, 2006;Miyazaki et al, 2016). The cause for the observed difference in body weight could be attributted to different DHEA regimes (de Heredia, et al, 2007), or due to different routes of DHEA administration that might lead to differences in circulating DHEA levels and differences in body weight (Miyazaki et al, 2016).…”