Androgens and Adipose Tissue
by Benjamin Bunting BA(Hons) PGCert
Written by Ben Bunting: BA, PGCert. (Sport & Exercise Nutrition) // British Army Physical Training Instructor // S&C Coach.
Androgens are male hormones that regulate body fat distribution. Androgens are produced by both the ovaries and adrenal glands and converted to testosterone and DHEA sulfate through conversion processes.
Androgens have been shown to bind and inhibit the action of androgen receptors found on preadipocytes, with total and free testosterone levels peaking around the time of ovulation for females.
Studies of skeletal muscle cells and surrounding fat cells have demonstrated that androgens stimulate muscle growth by binding to androgen receptors on muscle cells.
This interaction increases mRNA for enzymes required for protein synthesis as well as transport proteins used for moving amino acids in and out of cells, such as carnitine and creatine transport proteins.
Furthermore, androgens prevent the formation of triglycerides by increasing breakdown of fat within individual cells.
Androgens can influence the fat cells surrounding muscle cells by binding to androgen receptors on adipocytes.
This interaction causes them to shrink in size and become less lipid-laden, leading to less storage. Furthermore, these adipocytes produce hormones called adipokines that regulate fat metabolism and body weight through diet changes.
Research has also demonstrated that androgens are effective at decreasing fat cells' ability to store lipids by interrupting a signaling pathway normally used to support their functioning as adipocytes.
In addition, androgens may help reduce accumulation by increasing beta adrenergic receptors while simultaneously decreasing alpha adrenergic receptors which stimulate lipolysis.
Excessive androgen production in women can occur through hormonal imbalances, uterine fibroids, ovarian cysts, adrenal disorders (such as Cushing syndrome) and certain tumors.
Furthermore, some forms of birth control contain androgens in the form of progestin. A small study showed that users of progestin-only pills experienced significantly lower SHBG levels compared with estrogen-progestin combinations, suggesting it may affect fat tissue differently.
Adipose tissue, commonly referred to as fat, stores lipids in the form of triglycerides for energy storage purposes and is found throughout the body as padding and insulation.
Adipocytes store energy until used up for fuel use - these droplets swell when energy storage increases then they contract when energy needs decrease again.
Adipocytes may be found beneath the skin (subcutaneous fat tissue) or packed around organs and bone marrow (visceral fat), with numerous hormones controlling where and how much fat is stored.
Adipocytes serve as an organ of the endocrine system, producing numerous hormones that regulate metabolic activity in other tissues.
These include cytokines, proteins, specific lipids and miRNAs. Each providing signals about supply and demand through hunger/satisfaction cycles as well as responding to insulin by converting excess blood sugar to triglycerides.
These are then stored as fat, regulating cholesterol and inflammation responses, or signalling energy supply/demand cycles through hunger and satiety cycles.
Adipocytes also play a part in providing energy supply/demand signals through hunger/satisfaction cycles.
Then responding to insulin by converting excess blood sugar to triglycerides that are stored as fat cells as well as responding by producing excess blood sugar conversion as well as controlling cholesterol responses resulting in inflammation responses.
Researchers have unraveled the role of androgens in adipose tissue by exploring its cellular and molecular mechanisms of adipogenesis. They have demonstrated that human preadipocytes express high-affinity androgen receptors and that androgens inhibit adipogenesis.
Furthermore they demonstrated how angiogenesis and adipogenesis are reciprocally regulated via vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor-g (PPARg).
Men tend to store more visceral fat than women due to different levels of androgens circulating, particularly estrogen, which has been shown to negatively regulate fat mass accumulation.
Treatment of gonadally intact mice with estrogen or of male mice lacking an estrogen receptor with aromatase inhibitors was shown to effectively combat HFD-induced adipose tissue expansion and obesity, and reduce triglyceride accumulation while simultaneously inducing BAT thermogenesis.
Polycystic ovary syndrome (PCOS) patients tend to have high concentrations of androgens circulating in their system and, as a result, are at risk of diabetes and metabolic complications.
But the role of androgens in maintaining homeostasis of glucose may be more complicated; insulin resistance occurs more commonly among hypoandrogenemic females but not men.
Testosterone is the main androgen produced in males, and plays a critical role in their sexual development, including muscles and other secondary characteristics.
Levels of testosterone and other androgens in the body are tightly regulated by the pituitary gland in the brain.
Additionally, testosterone acts as the precursor for estrogen production both males and females alike - it converts to dihydrotestosterone which then becomes estradiol as its principal source.
Testicular androgen production increases with puberty. Once adulthood arrives, testosterone is converted to dihydrotestosterone (DHT) by an enzyme known as 5 alpha-reductase and converted back to testosterone.
Both compounds still possess androgenic activity though not to the same degree as its parent compound.
DHT also exhibits some degree of androgenic activity, though not as strongly as testosterone itself. Testosterone can also be converted to estrogen in fat tissue, the ovaries or adrenal glands or both for men or women respectively.
Men with low levels of androgens in their body may experience multiple physical changes when androgen levels drop too low.
This can include decreased sexual desire or inability to achieve an erection, increased body fat accumulation, diminished muscle bulk and strength, reduced bone density density and tender or swollen breasts (gynecomastia).
Furthermore, low testosterone may alter menstrual cycles by leading to irregular periods with heavier bleeding or more frequent or longer-lasting erections than usual.
Some individuals use synthetic forms of androgens known as anabolic steroids to increase muscle mass and enhance athletic performance.
However, such practices are considered form of doping by many sports leagues and should therefore be strictly prohibited.
Low levels of androgens can have adverse effects on men's mood, mental ability and sleep habits - leading to changes such as irritability, fatigue, weakness, inability to concentrate and depression.
Furthermore, this low androgen levels could influence heart rate and blood pressure as well as cell membrane movement across cell membranes.
Leptin is an essential adipose tissue hormone with impacts on energy homeostasis and neuroendocrine function in humans.
Low levels of leptin have been linked with obesity and other metabolic conditions; healthy adults should aim for 3 ng/mL or higher as their normal range.
Food deprivation reduces testosterone and LH levels in mice, delaying vaginal estrus; exogenous leptin administration restores these changes.
Additionally, it helps regulate triglyceride and free fatty acid levels in adipose tissue - often associated with hormonal disruption and subsequent weight gain in humans.
Leptin plays an essential role in reproductive physiology by communicating to the brain when sufficient energy stores have been stored in fat tissue, signaling to it when sufficient reserves have been attained and possibly contributing to puberty for children while supporting reproductive functions as we age.
Studies on patients with organic or genetic idiopathic hypogonadism, and those with functional hypogonadotropic hypogonadism, have demonstrated that fasting reduces LH pulsatility while simultaneously increasing serum testosterone, luteinizing hormone metabolites, gnRH, and androgen-binding protein concentrations.
Reintroducing testosterone via testosterone replacement therapy (TRT) reverses any metabolic alterations associated with hypogonadism-related metabolic alterations.
Uncertainty exists as to whether the metabolic abnormalities associated with Hypo-H arise directly from deficient production, secretion, or action of adipose tissue gonadotrophins.
Likewaise, whether they result from reduced testosterone and altered metabolism resulting in decreased production and secretion of gonadotropins.
Further studies are necessary to establish both pathogenetic roles attributed to hyperplasia in Hypo-H and metabolic changes attributed to functional hypogonadotropic hypogonadism as well as any reciprocal effects that correction has on androgenic function.
Testosterone deficiency leads to insulin resistance among healthy young men, while GnRH deficiency does not significantly impact glucose tolerance or fasting insulin and glycated hemoglobin (HOMA-IR).
Insulin resistance could be due to other metabolic abnormalities in these populations such as increased triglycerides or adipocyte proliferation, while those living with Hypo-H are resistant to insulin signaling due to upregulation of lipid phosphatase inhibitor which promotes lipoprotein synthesis while inhibiting fat breakdown.
Androgens and Lean Body Mass
Men, particularly, benefit from androgens because of their anabolic effect in stimulating protein synthesis in their skeletal muscles, thus decreasing body fat while simultaneously increasing lean body mass.
Unfortunately, as men age their levels of androgen decline leading to frailty and osteoporosis.
As people age, protein synthesis slows and fat storage increases. This imbalance between adipose tissue and muscle mass is known as sarcopenia and contributes significantly to impaired functioning in older people.
Research shows that androgens may play an essential role in combatting this condition through anabolic effects on skeletal muscle.
Sex steroids work by stimulating nuclear hormone receptors known as androgen receptors to control gene transcription, modulating metabolic processes such as lipolysis, fatty acid uptake and adipocyte development.
Androgens have long been recognized to increase both muscle mass and strength among both young and elderly individuals, helping prevent frailty and improving physical function.
One recent study randomly assigned healthy young and elderly male subjects 600 milligrams per week of either nandrolone or placebo over 12 weeks.
Researchers then measured maximum strength (the amount of weight that a person could lift using leg presses or squats), body fat content, bone mineral density measured using dual energy X-ray absorptiometry).
Results demonstrated that Nandrolone increased muscle mass and reduced fat in the thighs and abdomen significantly while improving thigh bone density, leg muscle mass, grip strength and bone mineral density in older males.
As such, authors concluded that this therapy can effectively and safely treat sarcopenia in males as they age.
Furthermore, researchers discovered that postmenopausal women not producing androgens produced similar benefits from oral oestrogens similar to Nandrolone in terms of bone and muscle density gains while decreasing abdominal fat by inhibiting Adipocyte growth while increasing lipolysis.
Thus concluding it being an effective and safe therapy against improving sarcopenia in postmenopausal women not producing androgens through inhibiting Adipocyte growth and increasing lipolysis thereby decreasing abdominal fat accumulation.
Androgens play an incredible role in human physiology. Research shows that they stimulate male reproductive organ growth, muscle growth, skin pigmentation (including hirsutism in men), hair growth ( including hirsutism in men) and production of sweat and sebum as well as reducing fat tissues.
Not withstanding blood coagulation, protein production, bone growth/density regulation/kidney size regulation as well as metabolism of cholesterol/glucose respectively.
In addition to their direct impact on liver lipid metabolism by inhibiting lipolysis/increasing fatty acid oxidation/decreasing triglyceride formation.
Women can convert androgens to estrogens through aromatase enzyme, while both types are then processed through the cytochrome P450 family of enzymes for metabolism.
This conversion occurs within their reproductive organs such as the ovaries and adrenal glands but may also occur via fat cells via aromatase production.
Because testosterone and other androgens affect the characteristics of muscle growth and increase lipolysis, athletes and body builders often utilize anabolic effects of androgens for performance enhancement purposes.