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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #254897
Title: Inflammatory phenotyping identifies CD11d as a gene markedly induced in white adipose tissue in obesity

Author
item THOMAS, ANTHONY - University Of California
item DUNN, TAMARA - University Of California
item Oort, Pieter
item GRINO, MICHEL - University Of The Mediterranean
item Adams, Sean

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/4/2011
Publication Date: 4/20/2011
Citation: Thomas, A.P., Dunn, T.N., Oort, P.J., Grino, M., Adams, S.H. 2011. Inflammatory phenotyping identifies CD11d as a gene markedly induced in white adipose tissue in obesity. Journal of Nutrition. 1172-1180.

Interpretive Summary: Obesity is associated with increased risk of developing poor blood sugar control (insulin resistance, type 2 diabetes) and cardiovascular disease. Chronic inflammation is believed to play a role in driving development of metabolic diseases, and the white adipose tissue (WAT, or fat tissue) of the body is now recognized as an important site of this inflammation. Furthermore, immune cells termed macrophages are thought to be the cells that interact with WAT fat cells to elicit pro-inflammatory signals. The latter can be measured by monitoring expression levels of various factors including integrins such as CD11 and CD68. Most studies of these issues have focused on a single level of fat to trigger obesity, inflammation, and metabolic changes, and most often at extremely high levels (i.e., 60% of calories). Thus, less is known about the inflammatory phenotype of more moderate obesity. In this study we measured inflammation and metabolism profiles in WAT and systemically in mice fed varying levels of fat (as calories) from 10%, 45%, and 60%, and discovered that a specific marker, CD11d, is massively increased in its expression in WAT of obese mice. More moderate fat feeding led to an intermediate degree of inflammation and metabolic perturbation, indicating that even more modest obesity is characterized by disruptions in normal immune and metabolic function.

Technical Abstract: In severe obesity, white adipose tissue (WAT) inflammation and macrophage infiltration are believed to contribute to WAT and whole-body insulin resistance. Specific players involved in triggering and maintaining inflammation (i.e., those regulating adipokine release and WAT macrophage recruitment, retention, or function) remain to be fully elaborated, and the degree to which moderate obesity promotes WAT inflammation remains to be clarified further. Therefore, we characterized adiposity and metabolic phenotypes in adult male C57BL/6J mice fed differing levels of dietary fat for 12 wk, concurrent with determinations of WAT inflammation markers and mRNA expression of leukocyte-derived integrins (CD11b, CD11c, CD11d) involved in macrophage extravasation and tissue macrophage homing/retention. As expected, a lard-based very high fat diet (60% kcal from fat) significantly increased adiposity and glucose intolerance vs. 10% fat-fed controls, coincident with higher retroperitoneal WAT transcript levels for pro-inflammatory factors and macrophage markers (i.e., tumor necrosis factor-a [TNFa] and CD68 mRNAs 3- and 5-fold of control levels, respectively, P<0.001). Mice fed a 45% fat diet had more moderate obesity, less glucose intolerance, and lower WAT macrophage/inflammatory marker mRNA abundances vs. 60% fat fed mice (i.e., TNFa and CD68 were 2-fold of control levels, P<0.01). WAT expression of CD11d was massively induced by obesity to an extent greater than any inflammatory marker described to date (to >50-fold of controls in high fat groups; P<0.0001), and this induction was WAT-specific. Since CD11d expression was also increased in retroperitoneal WAT of Zucker obese rats and in the subcutaneous WAT of obese adult women, this appears to be a common feature of obesity. Strong correlations of WAT CD11d transcript abundance with body weight in normal to modestly-obese mice (r=0.72 to r=0.80; P<0.01) raises an interesting possibility that activities of at least some WAT macrophages are closely linked to normal adipose remodeling that is a requisite for changes in WAT energy storage capacity.