Regulation of Energy Expenditure by NF-kB. NF-kB is a transcription factor that is activated in adipose tissue in obesity. NF-kB induces cytokine expression and inhibits lipid accumulation in adipocytes, which contribute to the pathogenesis of insulin resistance according to data derived from cellular models. To test the NF-kB activity in vivo, we enhanced and decreased NF-kB activity by overexpressing and knocking out of the p65 subunit. Fat-selective NF-kB activation induced a low grade inflammatory response in the fat tissue, and inhibited adiposity in the aP2-p65 mice. However, the inflammation did not impair systemic insulin sensitivity in the mice on either chow or high fat diet. The mice exhibited an increase in energy expenditure at room temperature and an elevation in thermogenesis in the cold environment. In fat-selective p65-KO mice, the thermogenesis was significantly impaired in the cold response leading to hypothermia in mice. The thermogenic alterations were associated with functional changes in brown adipose tissue (BAT) and white adipose tissues (WAT). The preliminary data suggests that NF-kB activation in adipose tissue may promote thermogenesis by enhancing BAT function and WAT browning. This possibility will be tested in three aims. The study will uncover the NF-kB activity in brown adipocytes and beige adipocytes for the first time. The results may provide answers to observations that the anti-inflammation therapies induce weight gain in humans, failure of anti-inflammatory therapy in insulin sensitization in most clinical trials, and disassociation of inflammation with insulin resistance in rodent models.

Public Health Relevance

Obesity increases risk of type 2 diabetes through impairing insulin action, a phenomenon called insulin resistance in the pathogenesis of type 2 diabetes. Animal study suggests that insulin resistance is a result of chronic inflammation in obesity. However, the human studies suggest that inflammation is not a major cause of insulin resistance. It is not known why there is a discrepancy in the role of inflammation. In this study, we will address this issue by studying the beneficial effects of inflammation using transgenic mice of NF-kB.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
High Priority, Short Term Project Award (R56)
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Cellular Aspects of Diabetes and Obesity Study Section (CADO)
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Abraham, Kristin M
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Lsu Pennington Biomedical Research Center
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Baton Rouge
United States
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Lee, J H; Zhang, Y; Zhao, Z et al. (2017) Intracellular ATP in balance of pro- and anti-inflammatory cytokines in adipose tissue with and without tissue expansion. Int J Obes (Lond) 41:645-651
Sun, Jingquan; Ye, Xin; Xie, Minhao et al. (2016) Induction of triglyceride accumulation and mitochondrial maintenance in muscle cells by lactate. Sci Rep 6:33732
Hao, Z; Mumphrey, M B; Morrison, C D et al. (2016) Does gastric bypass surgery change body weight set point? Int J Obes Suppl 6:S37-S43
Lu, H; Gao, Z; Zhao, Z et al. (2016) Transient hypoxia reprograms differentiating adipocytes for enhanced insulin sensitivity and triglyceride accumulation. Int J Obes (Lond) 40:121-8
Karkeni, Esma; Astier, Julien; Tourniaire, Franck et al. (2016) Obesity-associated Inflammation Induces microRNA-155 Expression in Adipocytes and Adipose Tissue: Outcome on Adipocyte Function. J Clin Endocrinol Metab 101:1615-26
Xu, Fen; Zheng, Xiaobin; Lin, Beisi et al. (2016) Diet-induced obesity and insulin resistance are associated with brown fat degeneration in SIRT1-deficient mice. Obesity (Silver Spring) 24:634-42
Zhang, Yong; Zhao, Zhiyun; Ke, Bilun et al. (2016) Induction of Posttranslational Modifications of Mitochondrial Proteins by ATP Contributes to Negative Regulation of Mitochondrial Function. PLoS One 11:e0150454
Mumphrey, M B; Hao, Z; Townsend, R L et al. (2016) Eating in mice with gastric bypass surgery causes exaggerated activation of brainstem anorexia circuit. Int J Obes (Lond) 40:921-8
Hao, Z; M├╝nzberg, H; Rezai-Zadeh, K et al. (2015) Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery. Int J Obes (Lond) 39:798-805
Goldsmith, Felicia; Keenan, Michael J; Raggio, Anne M et al. (2015) Induction of Energy Expenditure by Sitagliptin Is Dependent on GLP-1 Receptor. PLoS One 10:e0126177

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