|Alderete, Tanya L.|
|Hasson, Rebecca E.|
|Adam, Tanja C.|
|Kim, Joon Sung|
|Greenberg, Andrew S.|
|Goran, Michae I.|
Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/26/2011
Publication Date: 11/1/2011
Citation: Le, K., Mahurkar, S., Alderete, T., Hasson, R., Adam, T., Kim, J., Beale, E., Xie, C., Greenberg, A., Allayee, H., Goran, M. 2011. Subcutaneous adipose tissue macropage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kB stress pathway. Diabetes. 60(11):2802-2809. Interpretive Summary: We investigated why certain obese individuals have reduced ability to regulate blood glucose while other obese individuals have normal blood glucose values. Based upon prior studies in obese rodents, we predicted that an increase in the number of specialized cells, called macrophages, in fat tissue will be associated with increased blood glucose levels. When macrophages accumulate in fat tissue it has been suggested that they release substances that increase the accumulation of fat in the liver and the abdomen and increase blood glucose. To address these hypotheses, we performed fat biopsies on African-American and Hispanic obese young adults and correlated macrophage number with fat accumulation in the liver and abdomen. We found, that those Hispanic and African-American males and females, who had increased levels of macrophages in their fat tissue, also had increased fat accumulation in their abdomens and livers, and alterations in their blood glucose levels. However, those obese individuals who did not have increased numbers of macrophages in their fat tissue had less fat accumulation in their livers and abdomen and had improved blood glucose values. Future studies will investigate how these different diets can decrease the number of macrophages and improve blood glucose.
Technical Abstract: The goal was to examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), Beta-cell function, and SAT gene expression. SAT biopsies were obtained from 36 obese young adults (20 Hispanics, 16 African Americans) to measure crown-like structures (CLS), reflecting SAT inflammation. SAT, VAT, and HFF were measured by magnetic resonance imaging, and SI and Beta-cell function (disposition index [DI]) were measured by intravenous glucose tolerance test. SAT gene expression was assessed using Illumina microarrays. Participants with CLS in SAT (n = 16) were similar to those without CLS in terms of ethnicity, sex, and total body fat. Individuals with CLS had greater VAT (3.7 +/-1.3 vs. 2.6 +/- 1.6 L; P = 0.04), HFF (9.9 +/- 7.3 vs. 5.8 +/- 4.4%; P = 0.03), tumor necrosis factor-alpha (20.8 +/- 4.8 vs. 16.2 +/- 5.8 pg/mL; P = 0.01), fasting insulin (20.9 +/- 10.6 vs. 9.7 +/- 6.6 mU/mL; P < 0.001) and glucose (94.4 +/- 9.3 vs. 86.8 +/- 5.3 mg/dL; P = 0.005), and lower DI (1,559 +/- 984 vs. 2,024 +/-829 × 10(-4) min(-1); P = 0.03). Individuals with CLS in SAT exhibited upregulation of matrix metalloproteinase-9 and monocyte antigen CD14 genes, as well as several other genes belonging to the nuclear factor-kB (NF-kB) stress pathway. We concluded that adipose tissue inflammation was equally distributed between sexes and ethnicities. It was associated with partitioning of fat toward VAT and the liver and altered ß-cell function, independent of total adiposity. Several genes belonging to the NF-'B stress pathway were upregulated, suggesting stimulation of proinflammatory mediators.