Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue
Aliki Kosteli, … , Rudolf Zechner, Anthony W. Ferrante Jr.
Aliki Kosteli, … , Rudolf Zechner, Anthony W. Ferrante Jr.
Published September 27, 2010
Citation Information: J Clin Invest. 2010;120(10):3466-3479. https://doi.org/10.1172/JCI42845.
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Research Article

Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue

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.

Authors

Aliki Kosteli, Eiji Sugaru, Guenter Haemmerle, Jayne F. Martin, Jason Lei, Rudolf Zechner, Anthony W. Ferrante Jr.

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Figure 4

Lipolysis inhibition through dietary manipulation limits ATM accumulation during early weight loss.

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Lipolysis inhibition through dietary manipulation limits ATM accumulatio...
A caloric restriction protocol was used to induce weight loss with lower rates of lipolysis compared with caloric restriction of mice on a high-fat diet. High-fat diet–induced obese mice were fed 70% of their ad libitum caloric intake for 3 days in the form of either a diet high in carbohydrate or fat content. (A) Serum FFA in mice during weight loss induced by caloric restriction on a diet high in either fat or carbohydrate content. n = 5–6 mice/group. (B) Perigonadal adipose tissue sections from mice during weight loss induced by a diet high in fat (left panel) or high in carbohydrate content (right panel). Arrows indicate ATMs. Scale bars: 50 μm. (C) Macrophages as a percentage of all cells in perigonadal adipose tissue from mice during weight loss induced by caloric restriction on a diet high in either fat or carbohydrate content. n = 5–6 mice/group. *P < 0.05, versus calorie restriction on HFD. All data are represented as mean ± SD.