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Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow–derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-α expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals

Most sham feeding studies show that about three sham feeding tests are required for intake to reach maximum. One study, however, using a dilute solution, reported maximum sham intake in the first sham feeding test, suggesting that the progressive rise in sham intake may be concentration dependent. We tested this hypothesis with six groups of rats given five sham feeding tests each with one of six concentrations of sweetened condensed milk (0.5:1, 1:1, 2:1, 4:1, 8:1, 16:1, water-to-milk dilutions). It took three sham tests for intake to reach maximum with the three most concentrated solutions, but only one with the three weakest. Thus the intake of concentrated solutions of milk is limited by two negative feedback signals, one derived from the accumulation of fluid in the gastrointestinal tract, the other from a labile signal that loses its effectiveness with sham feeding experience. In contrast, the intake of weak concentrations is limited only by the nonlabile negative feedback signal because the labile signal is missing.

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