BIOHW 14 |
| Weight reduction is accompanied by metabolic adaptations that promote weight regain. We have modeled human weight regain in a rodent paradigm to study the adaptations in peripheral fuel utilization. Obese rats with a polygenic predisposition for obesity were weight reduced with an energy-restricted, low fat diet for up to 16 weeks and then allowed to relapse with ad libitum feeding. A combination of whole-body and tissue-specific analyses was performed to assess the utilization of fuels in this experimental paradigm. Weight-reduction improved insulin sensitivity and enhanced metabolic flexibility. In skeletal muscle, weight reduction induced a shift in the expression of metabolic pathway genes that favored the uptake and oxidation of glucose and minimized the uptake and oxidation of fats. In visceral fat, newly differentiated adipocytes appeared in the early stages of regain that could preferentially store ingested fat and ultimately expand the visceral lipid storage capacity. In the liver, periportal macrovesicular steatosis developed early in regain with minimal glycogen accumulation. Using ingested tracer studies during regain, we confirmed that ingested carbohydrate becomes the primary fuel for energy needs with excess carbohydrate preferentially directed to lipogenic, rather than glycogenic, pathways. Ingested fats are preferentially trafficked to hyperplasic visceral adipose depots and periportal regions in the liver. In all three tissues, the induction of sterol response element binding protein 1c is likely to be an important mediator of the tissue-specific shift in fuel utilization during regain. In summary, coordinated adaptations in skeletal muscle, adipose tissue, and liver create a flexible state of metabolism that utilizes and stores ingested fuels in a rapid, efficient manner. The rapidity of this clearance may impact nutrient sensing systems to promote subsequent bouts of feeding and continued regain. |
|
Genomics of Obesity
1:30 PM-4:45 PM, Tuesday, August 21, 2007 BCEC -- 203, Oral
Biotechnology of Health and Wellness |