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Very low calorie diet makes adipocytes “scream”
look at tissue samples for changes in glucose transport directly.” Marc Hellerstein, a physiologist at the After several weeks on a very low caloUniversity of California Berkeley, praised rie diet, fat cells are under stress and the study’s “solid” experimental design, hungry to replace what they’ve lost. noting that the 3-week interval after the That stress is reflected in the fat cells’ very low calorie diet allowed the authors protein expression profiles, Edwin Mato remove the immediate effects of a negariman and colleagues from Maastricht tive energy balance. University (MU; The Netherlands) and “Identifying the group of proteins inHasselt University (Belgium) report in volved in glucose transport JPR (2009, DOI 10.1021/ may have been the most usepr900606m). ful result here, because that Public-health authorigenerates a hypothesis they ties in many countries can go back and test,” he have identified obesity as notes. “But as potential a growing concern. Limitbiomarkers, nothing really ing food intake will usustands out, besides perhaps ally result in weight loss FABP4. Many of the changes and may reduce a perthey observed in blood lipids son’s blood sugar or or in known proteins such as blood pressuresin the leptin would be more short term. But as milstraightforward to measure.” lions of dieters can attest, Enzo Nisoli, an obesity retransforming short-term searcher at the University of weight loss into longMilan (Italy), says it was valuterm change is able to learn that the physichallenging. ological responses in adipose To gain insight into the tissue to a low-calorie diet metabolic changes that Changes in adipocyte proteins after weight loss reflect both increased glucose persist for 3 weeks after the come after short-term and fatty acid uptake and reduced inflammation. dietary intervention. “To me, weight loss, Mariman, a this is important information functional geneticist, and because it implies that the changes can be group, tubulin-β 5 and annexin A2, his co-worker Freek Bouwman collong-lasting,” he says. have functional links to GLUT4 as laborated with MU physiologists to He suggests segregating study subwell. study the best diets for maintenance jects by gender to isolate possible A fourth protein increased in exafter initial weight loss. A subgroup metabolic differences. Also, he says pression on average: fatty acid bindof 8 overweight and obese volunteers that doctors in some countries do not ing protein 4, which several papers willing to undergo biopsies contribfavor the 500-calorie/day diet used in have identified as a key mediator of uted tissue samples 3 weeks after the study. The type of caloric restricfatty acid metabolism and uptake. spending 5 weeks on a very low calotion that has been shown to prolong Others that changed significantly afrie diet. life span and stimulate mitochondrial ter the dietary intervention suggest During the 5-week weight-loss pefunction in laboratory animals is less decreased inflammation and oxidariod, study participants were limited severe, Nisoli adds. tive stress in adipose tissue. to 500 calories per day plus unlimited Mariman says his group’s future The results suggest that after shortvegetables. On average, they lost plans include recording subjects’ geterm weight loss, uptake of glucose close to 10 kg, most of it fat. netic markers and incorporating inforand fatty acids in adipocytes may inBiopsy samples were analyzed on mation about the differences between crease to compensate. The finding 2D gels, and protein identities were individuals who are low versus high could partially explain the often-obconfirmed by MALDI TOFMS. The fatty acid oxidizers. served tendency for dieters’ weights authors limited their analysis to pro“It was surprising that we were able to rebound after the diet is over, Matein spots present in samples from to find that some of the spots changed riman and Bouwman say. purified adipocytes and not present in the same direction in everybody,” “When you lose a significant in blood cells. Of >500 identifiable Mariman says. “Humans are very difamount of weight, your adipocytes spots from the tissue samples, ∼100 ferent from each other in their metaare screaming to take up glucose and were adipocyte-specific, and only 7 bolic responses.” fatty acids and store fat again,” he showed significant expression —Quinn Eastman says. “We would like to go back and changes on average.
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Of those seven, just three proteinssall of them related to glucose transportschanged in the same direction in all subjects. One enzyme that was reduced after the dietary intervention was fructose-bisphosphate aldolase C, a metabolic enzyme that has a role in tethering the glucose transporter GLUT4 to the cytoskeleton. The other two members of the
Journal of Proteome Research • Vol. 8, No. 12, 2009
10.1021/pr900986d
© 2009 American Chemical Society
