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1.
J Clin Invest ; 120(10): 3466-79, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20877011

ABSTRACT

Obesity elicits an immune response characterized by myeloid cell recruitment to key metabolic organs, including adipose tissue. However, the response of immune cells to nonpathologic metabolic stimuli has been less well studied, and the factors that regulate the metabolic-dependent accumulation of immune cells are incompletely understood. Here we characterized the response of adipose tissue macrophages (ATMs) to weight loss and fasting in mice and identified a role for lipolysis in ATM recruitment and accumulation. We found that the immune response to weight loss was dynamic; caloric restriction of high-fat diet-fed mice led to an initial increase in ATM recruitment, whereas ATM content decreased following an extended period of weight loss. The peak in ATM number coincided with the peak in the circulating concentrations of FFA and adipose tissue lipolysis, suggesting that lipolysis drives ATM accumulation. Indeed, fasting or pharmacologically induced lipolysis rapidly increased ATM accumulation, adipose tissue chemoattractant activity, and lipid uptake by ATMs. Conversely, dietary and genetic manipulations that reduced lipolysis decreased ATM accumulation. Depletion of macrophages in adipose tissue cultures increased expression of adipose triglyceride lipase and genes regulated by FFA, and increased lipolysis. These data suggest that local lipid fluxes are central regulators of ATM recruitment and that once recruited, ATMs form lipid-laden macrophages that can buffer local increases in lipid concentration.


Subject(s)
Adipose Tissue/immunology , Lipolysis/immunology , Weight Loss/immunology , Adipose Tissue/metabolism , Animals , Carboxylic Ester Hydrolases/physiology , Cell Movement , Fatty Acids, Nonesterified/blood , Lipase , Macrophages/physiology , Male , Mice , Mice, Inbred C57BL
2.
Metabolism ; 56(12): 1699-707, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17998024

ABSTRACT

Previous studies have linked overweight to lower milk and calcium consumption and have proposed a role of milk consumption on energy expenditure (EE). The goal of this study was to compare EE and food intake after a meal of either mixed-nutrient or single-nutrient beverage and examine whether supplementation with that beverage for 1 week will impact EE. This was a randomized, controlled crossover study testing the effect of 2 beverages, milk or fruit-flavored beverage, before and after a supplementation period of 1 week on EE. Food intake at a meal after a snack intake of each beverage was assessed at the end of each measurement period. Ten children, aged 9 to 10 years, participated in all of the testing sessions in the study. There was a significant beverage by testing day interaction on daily EE and thermic effect of food (TEF), whereby EE was greater with milk consumption relative to the fruit-flavored beverage on day 8 (P = .0014) and with fruit-flavored beverage consumption on day 1 vs day 8 (P = .01). Similarly, the TEF was greater with milk compared with fruit-flavored beverage consumption on day 8 (P = .0007) and with fruit-flavored beverage consumption on day 1 relative to day 8 (P = .0097). The TEF declined more rapidly during 6 hours after a fruit-flavored beverage than a milk meal (P = .0018). Food intake did not differ after snack consumption of each beverage before and after milk and fruit-flavored beverage supplementation periods. Over the longer term, consumption of milk beverages may have more favorable effects on energy balance in children than consumption of fruit-flavored beverages.


Subject(s)
Beverages , Energy Metabolism/physiology , Milk , Animals , Calcium/metabolism , Calorimetry, Indirect , Child , Cross-Over Studies , Dietary Supplements , Eating/physiology , Feeding Behavior/physiology , Female , Humans , Male , Respiratory Physiological Phenomena , Thermogenesis/physiology
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