The cellular structure and lipid/protein composition of adipose tissue surrounding chronically stimulated lymph nodes in rats

Abstract

To test the hypothesis that chronic immune stimulation of a peripheral lymph node induces the formation of additional mature adipocytes in adjacent adipose tissue, one popliteal lymph node of large male rats was stimulated by local injection of 10 microg or 20 microg lipopolysaccharide three times a week for 6 weeks. Adipocyte volumes in sites defined by their anatomical relations to the stimulated and homologous unstimulated popliteal lymph nodes were measured, plus adipocyte complement of the popliteal depot, and the lipid and protein content of adipocytes and adipose stroma. The higher dose of lipopolysaccharide doubled the mass of the locally stimulated lymph node and the surrounding adipose tissue enlarged by the appearance of additional mature adipocytes. Similar but smaller changes were observed in the popliteal adipose depot of the unstimulated leg and in a nodeless depot. The lipid content of the adipocytes decreased and that of the stroma increased dose-dependently in all samples measured but the changes were consistently greater in the depot surrounding the stimulated lymph node. The protein content of both adipocytes and stroma increased in samples surrounding the stimulated node. We conclude that chronic immune stimulation of lymphoid tissues induces the formation of more adipocytes in the adjacent adipose tissue. These findings suggest a mechanism for the selective hypertrophy of lymphoid-containing adipose depots in the HIV-associated adipose redistribution syndrome.

Fig. 1

Volume of perinodal (pn, darkest bars), middle (md, intermediate shading) and remote (re, palest bars) adipocytes from the popliteal adipose depots enclosing the stimulated (plain and speckled bars) and unstimulated (striped bars) popliteal lymph nodes, and that of perirenal adipocytes, following three injections per week for 6 weeks of 10 or 20 µg lipopolysaccharide, or saline. (A) Mean ± SE of adipocyte volume (nL). (B) Mean ± SE of the ratios of the volumes of popliteal adipocytes to that of perirenal adipocytes of the same rat. Each group, N = 18 large male rats. Differences between homologous samples from stimulated and unstimulated legs of the same rats significant at: *P < 0.05; **P < 0.01; ***P < 0.001.

Fig. 2

Numbers (means ± SE) of mature adipocytes (millions) in the popliteal adipose depots enclosing the stimulated (plain bars) and unstimulated (striped bars) popliteal lymph nodes, and in the perirenal depot, following three injections per week for 6 weeks of 10 or 20 µg lipopolysaccharide, or saline. Note that the values for the large perirenal depot have been divided by 10 to fit the data to the scale. Each group, N = 18 large male rats. Asterisk shows difference between homologous samples from stimulated and unstimulated legs of the same rats significant at P < 0.05; †, value significantly different at P < 0.05 from homologous sample of saline-injected controls.

Fig. 3

Means ± SE of lipid content (% fresh weight of adipose tissue) of the adipocytes and stroma from adipose tissue surrounding the stimulated and unstimulated popliteal lymph nodes, and that of perirenal adipocytes, following three injections per week for 6 weeks of 10 or 20 µg lipopolysaccharide, or saline. patterns and shading as in Fig. 1. (A) Isolated adipocytes; (B) stroma of adipose tissue. Each group, N = 18 large male rats. Differences between homologous samples from stimulated and unstimulated legs of the same rats significant at: *P < 0.05; **P < 0.01; ***P < 0.001.

Fig. 4

Means ± SE of protein content (mg/g fresh weight adipose tissue) of the adipocytes and stroma from the adipose tissue surrounding the stimulated and unstimulated popliteal lymph nodes, and that of perirenal adipocytes, following three injections per week for 6 weeks of 10 or 20 µg lipopolysaccharide, or saline. Bar patterns and shading as in Figs 1 and 3. (A) Isolated adipocytes; (B) stroma of adipose tissue. Each group, N = 18 large male rats. Differences between homologous samples from stimulated and unstimulated legs of the same rats significant at: *P < 0.05; **P < 0.01; ***P < 0.001.