Objectives: Basic science studies show that the extracellular matrix of adipose tissue, mainly represented by collagen VI, is dysfunctional in obesity and contributes to the development of the metabolic syndrome. We hypothesized in humans that increased collagen VI α3-subunit (COL6A3) mRNA is associated with adipose tissue macrophage chemotaxis and inflammation and that weight gain is accompanied by changes in the expression of COL6A3. Research Design and Methods: Adipose tissue biopsies were obtained from a cross-sectional study (n = 109), an overfeeding study (n = 9), and a pioglitazone treatment study (n = 14). Adipose tissue gene expression was measured by quantitative RT-PCR, immunohistochemistry, and adipocyte sizing by fixation with osmium and Coulter counting. Body composition was measured by dual-energy x-ray absorptiometry and visceral adipose tissue by computed tomography. Patients with high or low COL6A3 mRNA were compared by one-way ANOVA. Results: In humans, immunohistochemistry revealed that COL6 is present in adipose tissue extracellular matrix. COL6A3 mRNA is correlated with body mass index (r = 0.60, P < 0.0001) and fat mass (r = 0.41, P < 0.0001). COL6A3 expression was similar in obese vs. type 2 diabetes patients. Obese subjects with high COL6A3 mRNA had greater visceral adipose tissue mass (P < 0.05), lower size of small and medium adipocytes (P < 0.05), more CD68+ and CD163/MAC2+ macrophages, and increased macrophage inflammatory protein-1α and macrophage chemoattractant protein-1α mRNA (P < 0.05). Eight weeks of overfeeding increased body weight and COL6A3 mRNA (P < 0.05). Pioglitazone decreased COL6A3 mRNA, and the change was inversely proportional to baseline COL6A3 mRNA (r = −0.95, P < 0.0001). Conclusion: These results are consistent with basic science data, suggesting that COL6A3 might contribute to adipose tissue inflammation.

To study the metabolic activity of NF-κB, we investigated phenotypes of two different mouse models with elevated NF-κB activities. The transcriptional activity of NF-κB is enhanced either by overexpression of NF-κB p65 (RelA) in aP2-p65 mice or inactivation of NF-κB p50 (NF-κB1) through gene knock-out. In these models, energy expenditure was elevated in day and night time without a change in locomotion. The mice were resistant to adulthood obesity and diet-induced obesity without reduction in food intake. The adipose tissue growth and adipogenesis were inhibited by the elevated NF-κB activity. Peroxisome proliferator-activator receptor γ expression was reduced by NF-κB at the transcriptional level. The two models exhibited elevated inflammatory cytokines (tumor necrosis factor-α and interleukin-6) in adipose tissue and serum. However, insulin sensitivity was not reduced by the inflammation in the mice on a chow diet. On a high fat diet, the mice were protected from insulin resistance. The glucose infusion rate was increased more than 30% in the hyperinsulinemic-euglycemic clamp test. Our data suggest that the transcription factor NF-κB promotes energy expenditure and inhibits adipose tissue growth. The two effects lead to prevention of adulthood obesity and dietary obesity. The energy expenditure may lead to disassociation of inflammation with insulin resistance. The study indicates that inflammation may prevent insulin resistance by eliminating lipid accumulation.

The objective of this study was to determine whether nitric oxide (NO) is produced locally in the bovine corpus luteum (CL) and whether NO mediates p

More than 2.5 million patients in the U.S. require treatment for pressure ulcers annually, and the elderly are at particularly high risk for pressure ulcer development. Current therapy for pressure ulcers consists of conservative medical management for shallow lesions and aggressive debridement and surgery for deeper lesions. The current study uses a murine model to address the hypothesis that adipose-derived stromal/stem cell (ASC) treatment would accelerate and enhance pressure ulcer repair. The dorsal skin of both young (2 months old [mo]) and old (20 mo) C57BL/6J female mice was sandwiched between external magnets for 12 hours over 2 consecutive days to initiate a pressure ulcer. One day following the induction, mice were injected with ASCs isolated from congenic mice transgenic for the green fluorescent protein under a ubiquitous promoter. Relative to phosphate-buffered saline-treated controls, ASC-treated mice displayed a cell concentration-dependent acceleration of wound closure, improved epidermal/dermal architecture, increased adipogenesis, and reduced inflammatory cell infiltration. The ASC-induced improvements occurred in both young and elderly recipients, although the expression profile of angiogenic, immunomodulatory, and reparative mRNAs differed as a function of age. The results are consistent with clinical reports that fat grafting improved skin architecture in thermal injuries; the authors of this published study have invoked ASC-based mechanisms to account for their clinical outcomes. Thus, the current proof-of-principle study sets the stage for clinical translation of autologous and/or allogeneic ASC treatment of pressure ulcers. Significance: Adipose-derived stromal/stem cells (ASCs) promote the healing of pressure ulcer wounds in both young and old mice. ASCs enhance wound healing rates through adipogenic differentiation and regeneration of the underlying architecture of the skin.