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The increased use of HFCS in the United States mirrors the rapid increase in obesity

calorically sweetened beverages may enhance caloric overconsumption

Expression of PPARγ is highest in adipose tissue,

PPARγ also plays a key role in the entraining of adipose tissue lipid metabolism to nutritional state

Its expression is highest postprandially

its activation leads to upregulation of genes that mediate FA uptake and trapping

PPARγ may also promote futile cycling in adipocytes between triglyceride (TG) esterification and de-esterification

its high expression in macrophages, which are now known to infiltrate the dysfunctional adipose tissue of obese subjects

Other targets of HIF-1α include glucose transporter-1 (GLUT-1), the main transporter involved in glucose uptake [9,10]; lactate dehydrogenase V (LDHV), which is responsible for the conversion of pyruvate into lactate; pyruvate dehydrogenase kinase isozyme 1 (PDK1), which is responsible for the phosphorylation and consequent inactivation of pyruvate dehydrogenase (PDH); and carbonic anhydrase IX (CAIX), a hypoxia-related protein involved in pH regulation [11]. Alpha-methylacyl-CoA racemase (AMACR), pristanoyl-CoA oxidase (ACOX-3) and D-bifunctional protein (DBP), are also important fatty acid oxidation-related proteins in prostate cancer

the essential role played by the cross-talk between stroma and epithelium in carcinogenesis and prostate cancer progression has been increasingly recognised

strong membranous expression of MCT1 was consistently observed in cancer cells, suggesting a role for MCT1 in the transport of lactate into tumour cells from the acidic extracellular matrix, suggesting that lactate might be used as a fuel by oxidative cancer cells.

Our hypothesis is in agreement with those of Fiaschi et al.[17], who describe the metabolic reprogramming of CAFs towards the Warburg phenotype as a result of contact with prostate cancer cells

Using in vitro studies, they showed lactate production and efflux by de novo expressed MCT4 in CAFs and also demonstrated that, upon contact with CAFs, prostate cancer cells were reprogrammed towards aerobic metabolism, with an increase in lactate uptake via the lactate transporter MCT1.

pharmacological inhibition of MCT1-mediated lactate uptake dramatically affected PCa cell survival and tumour outgrowth

In this model, “energy transfer” or “metabolic coupling” between the tumour stroma and epithelial cancer cells fuels tumour growth and metastasis via oxidative mitochondrial metabolism in anabolic cancer cells

the concomitant expression of MCT1 in tumour cells and MCT4 in fibroblasts in the same tissue is clinically significant, and associated with poor prognosis.

insulin is an important inhibitor of the synthesis of SHBG

no correlation between leptin and SHBG levels

SHBG reduction in obesity is a minor determinant of lowered androgen levels

SHBG can explain only up to 3% of the correlation

testicular T de novo production is impaired in obese men and that leptin seems to be the best hormonal predictor of this blunted response to LH stimulation

The low basal 17-OH-P levels found in massively obese men are consistent with a global impairment of Leydig cell steroidogenic function in this group of subjects.

These findings indicate that obese men have a FM-related defect in the enzymatic conversion of 17-OH-P to T, which is revealed by hCG stimulation.

Other studies have investigated the adrenal function in male obesity and have shown that basal cortisol and 17-OH-progesterone levels tend to decrease with the increase in the degree of obesity

High E2 can inhibit the expression and activity of the 17,20-lyase and may be responsible for this steroidogenic lesion

However, stimulated E2 levels were not higher in the obese than in controls, excluding the fact that the lower androgen response was due to an increased aromatization of T to E2 and that estrogens have a major role in the observed defect of 17,20-lyase activity in obese men.

the percentage increase in the 17-OH-progesterone to T molar ratio paralleled the increase in leptin levels of obese men

Multiple regression analysis indicated that the best hormonal predictor of the obesity-related reduction in T and FT basal levels and androgen changes after hCG stimulation was serum leptin concentration

insulin has no negative influences on androgen production in obese men

insulin is known to have stimulatory actions on T production that have been demonstrated in obese and normal weight men (57) and in Leydig cells in culture

the negative correlation between insulin and basal T can be partly explained by the inhibitory action of insulin on SHBG production

hypogonadal men have higher circulating leptin levels compared with hypogonadal patients under effective androgen substitution therapy

The impaired androgen response to LH stimulus was due to a defect in the enzymatic conversion of 17-OH-progesterone to T, which was disclosed by a leptin-related increase in 17-OH-progesterone to T ratio

Estrogens, which are inhibitory modulators of LH pulsatility and bioactivity