Weight Loss Genetics – DHEA

Dehydroepiandrosterone (DHEA) is a natural steroid that tends to peak around age 25 and drop off rapidly in older people.This steroid is secreted by the adrenal cortex, and it is involved in a lipid (fat) catabolism.  Some studies have shown that DHEA reduces fat accumulation in mice fed a high-fat diet.

A recent (June 2016) study concluded: “Our results showed that long-term DHEA administration decreased body weight in rats on a high-fat diet.”  It goes on to discuss the pathways involved with DHEA and finds that: “Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol and glucogenic amino acids [38]. Phosphoenolpyruvate carboxykinase (PEPCK) is the rate-limiting enzyme in gluconeogenesis and which catalyzes the glucose synthesis from metabolic precursors [39]. We found that Pepck mRNA expression levels significantly decreased in the 50 and 100 mg·kg−1 DHEA treatment groups. As PEPCK is one of the key enzymes of gluconeogenesis, we speculated that DHEA treatment inhibited the generation of glucose by reducing Pepck mRNA expression. Several studies have demonstrated that DHEA can promote the absorption of glucose in fibroblasts [40], adipocytes [41], muscle [42] and hepatocytes [43]. In some glucose-sensitive tissues, such as liver and muscle, the transfer of glucose depends on the transporter of GLUT-2 and GLUT-4 [44, 45]. The present study showed that Glut2 mRNA expression levels in the 50 and 100 mg·kg−1 DHEA treatment groups, and Glut4 mRNA expression level in the 50 mg·kg−1 DHEA treatment group significantly increased in the rats on a high-fat diet”  [ref]

A small study in 2012 looked at the effect of DHEA-S (100mg/day) on women in regards to weight loss.  The women on DHEA-S did have weight loss, and those who were post-menopausal also had better results on their metabolic syndrome score.  [ref]

“Dehydroepiandrosterone (DHEA) exerts a wide variety of therapeutic effects against medical disorders, such as diabetes and obesity. However, the molecular basis of DHEA action remains to be clarified. Previously, we reported that DHEA-enhanced dual specificity protein phosphatase, designated DDSP, is one of the target molecules of DHEA. To examine the role of DDSP in DHEA signaling, we generated mice that carry a DDSP transgene in which expression is driven by the CAG promoter (DDSP-Tg). DDSP-Tg mice weighed significantly less than wild-type (WT) control mice when a high-fat diet was supplied (p < 0.01). No difference in food-intake or locomotor activity was found between DDSP-Tg and WT mice. Oxygen consumption of DDSP-Tg mice was higher than that of WT mice (p < 0.01), which suggested an increase in basal metabolism in DDSP-Tg mice. To further investigate the role of DDSP in genetically obese mice, DDSP-Tg mice with a db/db background were generated (DDSP-Tg db/db). We observed cancellation of obesity by the db/db mutation and development of a cachexic phenotype in DDSP-Tg db/db mice. In conclusion, our study shows that expression of DDSP leads to prevention of diet-induced and genetic (db/db) obesity. Anti-obese effects of DHEA might be mediated through DDSP, which might be a therapeutic target for intervention of obesity.”[ref]

The flip side is that to create a rat model of PCOS, rats are given DHEA.  Too much DHEA, whether naturally or through supplements, can cause side effects including facial hair and lowered voice in women. [ref]

DHEAS – Dehydroepiandrosterone sulfate – is the inactive precursor to DHEA, which then is converted into androgens and estrogens.  DHEAS concentrations are more stable and easier to measure accurately.

DHEAS Genes:

rs2185570 (C is the effect allele, CYP2C9 gene)

  • C is associated with lower DHEAS levels [ref]

rs17277546 (A is the effect allele, TRIM4 gene)

  • A is associated with lower DHEAS levels [ref]

rs182420 (C is the minor allele, SULT2A1)

  • C is associated with higher DHEAS levels in women [ref] and children [ref]

Raising DHEAS levels naturally:

  • “12 weeks of yogic training produces a significant increase in GH and DHEAS for both male and female groups as compared to their baseline data, whereas no as such changes were observed in the control group.” [ref]
  • DHEA supplements can be found at your local health food store or on Amazon.com. *

*Amazon affiliate link:  I link to the category listing for the supplement instead of a specific recommendation.  Please read the reviews and go with a brand that you are comfortable using.  

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