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

• Main Authors: Clarkson Priscilla M (Author), Angelopoulos Theodore J (Author), Price Thomas B (Author), Thompson Paul D (Author), Seip Richard L (Author), Hansen Barbara C (Author), Brandoli Cinzia (Author), Reeves Erica K (Author), Harmon Brennan (Author), Devaney Joseph (Author), Tesi-Rocha Carolina (Author), Bradbury Meg (Author), Gordish-Dressman Heather (Author), Uthurralt Julieta (Author), Moyna Niall M (Author), Pescatello Linda S (Author), Visich Paul S (Author), Zoeller Robert F (Author), Gordon Paul M (Author), Hoffman Eric P (Author)
• Format: Book
• Published: BMC, 2007-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<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>

Item Description

10.1186/1471-2350-8-55
1471-2350