PPARα L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

<p>Abstract</p> <p>Background</p> <p>Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components (typically 50–80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome.</p> <p>Methods</p> <p>We studied 610 young adult volunteers (average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training.</p> <p>Results</p> <p>We found the PPARα L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes (LL = 116 ± 11 mg/dL, LV = 208 ± 30 mg/dL; p = 0.004). Men with the V allele showed lower HDL (LL = 42 ± 1 mg/dL, LV = 34 ± 2 mg/dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume (LL = -1,707 ± 21 mm³, LV = 17,617 ± 58 mm³; p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARα L162V is on serum triglycerides, with downstream effects on adiposity and response to training.</p> <p>Conclusion</p> <p>Our results on association of PPARα and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% (p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males (p = 0.0037).</p

Sex difference in hepatic peroxisome proliferator-activated receptor alpha expression: influence of pituitary and gonadal hormones.

Peroxisome proliferator-activated receptor (PPAR) alpha is a nuclear receptor that is mainly expressed in tissues with a high degree of fatty acid oxidation such as liver, heart, and skeletal muscle. Unsaturated fatty acids, their derivatives, and fibrates activate PPARalpha. Male rats are more responsive to fibrates than female rats. We therefore wanted to investigate if there is a sex difference in PPARalpha expression. Male rats had higher levels of hepatic PPARalpha mRNA and protein than female rats. Fasting increased hepatic PPARalpha mRNA levels to a similar degree in both sexes. Gonadectomy of male rats decreased PPARalpha mRNA expression to similar levels as in intact and gonadectomized female rats. Hypophysectomy increased hepatic PPARalpha mRNA and protein levels. The increase in PPARalpha mRNA after hypophysectomy was more pronounced in females than in males. GH treatment decreased PPARalpha mRNA and protein levels, but the sex-differentiated secretory pattern of GH does not determine the sex-differentiated expression of PPARalpha. The expression of PPARalpha mRNA in heart or soleus muscle was not influenced by gender, gonadectomy, hypophysectomy, or GH treatment. In summary, pituitary-dependent hormones specifically regulate hepatic PPARalpha expression. Sex hormones regulate the sex difference in hepatic PPARalpha levels, but not via the sexually dimorphic GH secretory pattern

High-risk human papillomaviruses and epstein-barr virus presence and crosstalk in human oral carcinogenesis

Oral cancer is the most frequent type of malignancy of the head and neck area worldwide. This cancer is a major cause of mortality in several parts of the world especially in certain Asian countries. In fact, the majority of cancer deaths are the result of metastasis, either directly due to tumor involvement of critical organs or indirectly due to therapeutic side effects. On the other hand, it is estimated that 10–20% of human cancers are linked to virus infections including Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) especially types 16, 18, and 33, which cumulatively infect 80–90% of the population worldwide. Moreover, it has been reported that oncoproteins of high-risk HPV type 16 can covert noninvasive and nonmetastatic human cancer cells into invasive and metastatic form. It was pointed out that high-risk HPVs and EBV are important etiological factors in human oral cancer, since around 35 and 55% of these cancers are positive for these viruses, respectively. In addition, it was recently revealed that high-risk HPVs and EBV can be copresent in human oral cancer, and their copresence is associated with high-grade invasive carcinomas. Thus, it is evident that high-risk HPVs and EBV oncoproteins play an important role in the initiation and progression of human oral cancer. In this chapter, we will overview the presence and role of HPVs and EBV in this frequent malignancy, more specifically; we will focus on the role of their oncoproteins and their interactions with other oncogenes in human oral carcinogenesis.Scopu