Dehydroepiandrosterone Alters Zucker Rat Soleus and Cardiac Muscle Lipid Profiles

Abstract

High levels of serum free fatty acids (FFA) and lower proportions of polyunsaturated (PU) FAs, specifically arachidonic acid (AA), are common in obesity, insulin resistance (IR), and type 2 diabetes mellitus. Dehydrepiandrosterone (DHEA) decreases body fat content, dietary fat consumption, and insulin levels in obese Zucker rats (ZR), a genetic model of human youth onset obesity and type 2 diabetes. This study was conducted to investigate DHEA's effects on lean and obese ZR serum FFA levels and total lipid (TL) FA profiles in heart and soleus muscle. We postulated that DHEA alters serum FFA levels and tissue TL FA profiles of obese ZR so that they resemble the levels and profiles of lean ZR. If so, DHEA may directly or indirectly alter tissue lipids, FFA flux, and perhaps lower IR In obese ZR. Lean and obese male ZR were divided into six groups with 10 animals In each: obese ad libitum control, obese pair-fed, obese DHEA, lean ad libitum control, lean pair-fed, and lean DHEA. Ali animals had ad libitum access to a diet whose calories were 50% fat, 30% carbohydrate, and 20% protein. Only the diets of the DHEA treatment groups were supplemented with 0.6% DHEA. Pair-fed groups were given the average number of calories per day consumed by their corresponding DHEA group, and ad libitum groups had 24-h access to the DHEA-free diet. Serum FFA levels and heart and soleus TL FA profiles were measured. Serum FFA levels were higher in obese (-1 mmol/L) compared to lean (-0.6 mmol/L) ZR, regardless of group. In hearts, monounsaturated (MU) FA were greater and PU FA were proportionally lower In obese compared to the lean rats. In soleus, saturated and MU FA were greater and PU FA were proportionally lower in the obese compared to the lean rats. DHEA groups displayed significantly increased proportions of TL AA and decreased oleic acid in both muscle types. Mechanisms by which DHEA alters TL FA profiles are a reflection of changes occurring within specific lipid fractions such as FFA, phospholipid, and triglyceride. This study provides initial insights into DHEA's lipid altering effects.

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

“…By contrast, our experiment spanned a 13-week period that allowed us to observe a significant effect of DHEA on AT composition. Similarly to us, other authors have reported differences in FAs in muscle (Abadie et al 2001), liver (Imai et al 2001), and 3T3-L1 adipocytes (Gómez et al 2002) due to DHEA administration.…”

“…There is a previous work that reported no changes in rat AT fatty acids after 7 days of DHEA administration (Abadie et al 2001). However, due to the lower lipid turn-over rate of this tissue, a 7-day period may not be long enough to appreciate variations in FA profile in AT.…”

“…Despite this fact, little is known about the effects of DHEA on FA composition in different tissues (Abadie et al 2001, Imai et al 2001, Gómez et al 2002, and no studies to our knowledge have shown significant changes in AT fatty acid profile due to DHEA action.…”

“…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.…”

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

“…In contrast, others have suggested a role for DHEA-S treatment in fatmass loss (Nestler et al 1988). Furthermore, DHEA-S plasma levels show a negative correlation with visceral fat distribution in women (Garaulet et al 2000) and its administration seems to improve glucose tolerance (Haffner & Valdez, 1994;Richards et al 2000) and to reduce serum cholesterol and TAG (Macario et al 1999), so ameliorating these features of the metabolic syndrome.In rodents, DHEA has been reported to decrease dietary fat and energy intakes as well as body weight and fat content (Taniguchi et al 1995;Richards et al 1999;Pham et al 2000;Abadie et al 2001;Kajita et al 2003;Ryu et al 2003). However, the mechanisms of action of this hormone on body composition are not yet fully understood, although a role in food intake regulation has been suggested (Shepherd & Clearly, 1984;Abadie et al 1993;Svec et al 1995;Wright et al 1995;Svec & Porter, 1996;Pham et al 2000), or even in the utilisation or storage of ingested energy Mohan et al 1990).…”