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Got Fat? Pass the Testosterone Please!
by: Tom Rayhawk

Consider this: how many times have you read or heard that there is no such thing as a “cutting” steroid? For years the generally accepted doctrine was that steroids do not reduce adipose tissue but rather can decrease water retention and inhibit estrogen’s actions thus producing the “hard” look. Furthermore, the consensus seems to be that while testosterone and related anabolic substances certainly aid the dieting bodybuilder it is only via the androgen’s anti-proteolytic abilities, thus sparing muscle tissue while in a hypocaloric state, in addition to the aforementioned “drying out” effect.

In short – this is hogwash!! As this article will validate, an abundance of clinical research and peer-reviewed data strongly supports testosterone’s (T) fat reducing actions and its preventative impact on adipocyte generation (1,2,3). Therefore, T acts both in the breakdown of existing fat tissue and to hinder pre-adipocytes from maturing. CCAAT enhancer-binding proteins (CEBPs) are vital contributors at several stages of adipogenesis – or fat cell formation – from early uptake and accumulation of lipids to the differentiation, proliferation, and terminal production of the adipocyte. CEBPs exist in an alpha, sigma, and beta form. The beta and sigma form promote the transcription of PPARy2, which is arguably the most important factor in fat cell formation. CEBP possesses intrinsic pro-adipogenic activity independent of PPARy2. Specifically, the alpha and sigma isoform of CEBP interact with promoter regions of DNA involved in adipose development (5). PPARy2, stimulated by the CEBP isoforms, is capable of the same. This leads to a viscous cycle beginning with CEBP activity. DNA promotion of said adipogenic proteins follows, including PPARy2, which itself then activates the same lipid-related genes as the CCAAT enhancer-binding proteins. Testosterone has been shown to reduce all three forms of CEBP’s, which, predictably, curtails PPARy2 functions (5, 6, 7, 17, 23). Evidence exists as well that dihydrotestosterone shares T’s anti-CEBP characteristics (6, 23). Like muscle tissue, fat cells express anabolic receptors, which bind to respective androgens and initiate inhibitory effects on CEBP’s. Visceral Adipose Tissue (VAT) is more sensitive to T than subcutaneous fat (SC). This is most likely explained by the fact that AR’s occur in greater number in VAT versus SC tissue (2, 3, 4). T’s strong effect on VAT coincides with the observed reduction in abdominal fat in hypogonadal men placed on testosterone therapy. Furthermore, T’s antiadiogenic and lipolytic actions are more predominant in VAT (1, 2). Pre-adipocytes, located in VAT, show reduced activity of the CEBP’s when exposed to testosterone (5, 6). A novel observational study followed 511 males aged 30-79, over a 12-year period charting the effects of serum androstenedione, testosterone, and SHBG and their relation to VAT. Hormone analysis was conducted before and after this period and concluded that below normal androstenedione and testosterone show strong correlation with abdominal adipose tissue. (8). Peroxisomal proliferator-activated receptor gamma 2 is another protein that functions to increase the differentiation of adipocytes. Treatment with either testosterone or DHT reduces PPARg2 providing another means whereby androgens discourage the differentiation stage in adipogenesis (22) The metabolic alterations experienced in VAT due to testosterone are of significance with both negative and positive ramifications. Lipid uptake is inhibited in VAT mainly due to a decrease in lipoprotein-lipase activity, and a reduction in serum insulin and glucose levels (9). It should be noted that lipid uptake is enhanced by elevated hyperglycemia/hyperinsulinemia, primarily in VAT (10). So the decrease in VAT noted with a reduction of glucose/insulin levels – via testosterone elevation – should make sense. The ability of testosterone to stimulate fatty acid release from VAT can be problematic, though. Feeding directly into the liver via the portal vein, these fatty acids have the potential to impair both insulin sensitivity and function, induce hyperglycemia, and increase LDL levels. Ultimately this can lead to hyperinsulinemia, hyperglycemia, hyperlipidemia, and hypertension, vascular resistance, all of which are consistent with the pathology of “Metabolic Syndrome X” (11). In addition, cortisol, originating in VAT, is also released and fed to the liver via the portal vein. This exacerbates fat cell maturity as cortisol increases the differentiation of pre-adipocytes into the adult forms (13). It would seem logical then to suggest a cause and effect relationship between free fatty acid release from VAT by testosterone and the development the conditions of Metabolic Syndrome X. This may be a moot point though as testosterone treatment has been associated with an actual reduction in both total cholesterol and LDL levels. Previous studies indicate that testosterone – especially its chemically altered versions – can lower HDL levels deemed the “good cholesterol”. This has not been demonstrated conclusively, as results of other research efforts imply that T is neutral in regards to HDL, neither causing a significant increase or decrease (12, 16). In relation to the cardiovascular disorders, normal or slightly enhanced T levels might exert a protective effect. Pro-inflammatory cytokines TNF , IL-1ß, and IL-6 in human macrophages, are positively associated with congestive heart failure and atherosclerosis. Not only has testosterone been shown to reduce the elevations in these cytokines but also up regulates anti-inflammatory cytokines such as IL-10, leading to an improvement in improving overall cardiovascular function. (12, 14, 15) This decreases susceptibility to congestive heart failure and vascular disease also due in part to T’s vasodilating characteristics.

In relation to existing fat tissue, T levels are inversely associated with lipoprotein lipase, an enzyme involved in the breakdown of triglycerides and recycling of the resulting fatty acids and eventual production a mature lipid-rich adipocyte. Testosterone also impairs overall lipid uptake into fat cells, hindering hypertrophy of existing fat cells. T is positively correlated with beta receptor number catecholamine sensitivity, thus heightening thermogenesis (18, 19, 20). The thermogenic process involves a G-protein activation and a downstream production of lipolytic enzymes and proteins. Both DHT and Testosterone amplifies adenylate cyclase activity, an enzyme vital to beta receptor stimulated lipolysis (21). Moreover, hormone-sensitive lipase (HSL) initiates the breakdown of stored tryiglycerides into fatty acids, which can be oxidized and thus “burned” in either mitotochondria and/or peroxisomes. T not only elevates HSL but also Protein Kinase A, an enzyme that functions in the G-protein stimulated lipolysis (18, 20) By jacking up these lipolytic enzymes and proteins, beta oxidation occurs. Androgens also increase other such enzymes including carboxylesterase 3, acetyl-coenzyme A acyltransferase 1, 3-ketoacyl-CoA thiolase B and enoyl-coenzyme A hydratase/3-hydroxyacyl coenzyme A dehydrogenase (2, 24). Enzymes vital to lipogenesis, conversely, show a consistent negative correlation with both T and DHT. Malic enzyme, glyceraldehyde dehydrogenase (GDH), and fatty acid elongation factors – all capable of pro-lipogenic effects, are inhibited by DHT and T (2, 24) It is of great importance, though, to understand that the T’s positive benefits espoused in this article DO NOT apply to females. In fact, typically, the majority of natural male androgens, such as testosterone and DHT, exert converse or opposing actions – often negative – in females compared to males. Furthermore, the studies and research cited herein refer to inherent activity of endogenous T and DHT or hormone replacement therapy (HRT). These intrinsic natural androgens and their actions, thus, do not extend to chemical altered androgens or anabolic steroids. This does not necessarily imply that AAS do not have the potential to mimic endogenous male hormone. This just indicates that only research reviews examining naturally produced androgens were considered herein. If truth be told, a follow-up article delving even deeper into functions of T on obesity would certainly be justified. It also could review effects of both testosterone in females and chemically altered androgens. This article provides a fairly brief review of what is actually an impressive and growing body of evidence supporting Testosterone and other androgens as potent lipolytic and anti-adipogenic hormones. In fact, while the author had reviewed relevant literature beforehand describing the interactions of androgens and adipose, the additional dissection of this topic revealed a much greater than anticipated number of mechanisms and actions of natural androgens. Testosterone has not really received the respect and appreciation it deserves for its wide range of health benefits. Recently, though, with the ever-increasing administration of HRT to males and evidence confirming its potential benefits, the negative connotation and exaggerated drawbacks of such treatment is dying out. In its place exists a wealth of legitimate research claims and an increased priority placed on unbiased future studies.

References

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