The role of adipogenic capacity and dysfunctional subcutaneous adipose tissue in the inheritance of type 2 diabetes mellitus: cross-sectional study.

OBJECTIVE: This study tested the hypothesis that limited subcutaneous adipose tissue (SAT) expansion represents a primary predisposition to the development of type 2 diabetes mellitus (T2DM), independent of obesity, and identified novel markers of SAT dysfunction in the inheritance of T2DM. METHODS: First-degree relatives (FDR) of T2DM patients (n = 19) and control individuals (n = 19) without obesity (fat mass < 25%) were cross-sectionally compared. Body composition (bioimpedance, computed tomography) and insulin sensitivity (IS; oral glucose tolerance test, clamp) were measured. SAT obtained by needle biopsy was used to analyze adipocyte size, lipidome, mRNA expression, and inflammatory markers. Primary cultures of adipose precursors were analyzed for adipogenic capacity and metabolism. RESULTS: Compared with control individuals, FDR individuals had lower IS and a higher amount of visceral fat. However, SAT-derived adipose precursors did not differ in their ability to proliferate and differentiate or in metabolic parameters (lipolysis, mitochondrial oxidation). In SAT of FDR individuals, lipidomic and mRNA expression analysis revealed accumulation of triglycerides containing polyunsaturated fatty acids and increased mRNA expression of lysyl oxidase (LOX). These parameters correlated with IS, visceral fat accumulation, and mRNA expression of inflammatory and cellular stress genes. CONCLUSIONS: The intrinsic adipogenic potential of SAT is not affected by a family history of T2DM. However, alterations in LOX mRNA and polyunsaturated fatty acids in triacylglycerols are likely related to the risk of developing T2DM independent of obesity.

Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors.

Later stages of secondary lymphedema are associated with the massive deposition of adipose tissue (AT). The factors driving lymphedema-associated AT (LAT) expansion in humans remain rather elusive. We hypothesized that LAT expansion could be based on alterations of metabolic, adipogenic, immune and/or angiogenic qualities of AT. AT samples were acquired from upper limbs of 11 women with unilateral breast cancer-related lymphedema and 11 healthy women without lymphedema. Additional control group of 11 female breast cancer survivors without lymphedema was used to assess systemic effects of lymphedema. AT was analysed for adipocyte size, lipolysis, angiogenesis, secretion of cytokines, immune and stem cell content and mRNA gene expression. Further, adipose precursors were isolated and tested for their proliferative and adipogenic capacity. The effect of undrained LAT- derived fluid on adipogenesis was also examined. Lymphedema did not have apparent systemic effect on metabolism and cytokine levels, but it was linked with higher lymphocyte numbers and altered levels of several miRNAs in blood. LAT showed higher basal lipolysis, (lymph)angiogenic capacity and secretion of inflammatory cytokines when compared to healthy AT. LAT contained more activated CD4+ T lymphocytes than healthy AT. mRNA levels of (lymph)angiogenic markers were deregulated in LAT and correlated with markers of lipolysis. In vitro, adipose cells derived from LAT did not differ in their proliferative, adipogenic, lipogenic and lipolytic potential from cells derived from healthy AT. Nevertheless, exposition of preadipocytes to LAT-derived fluid improved their adipogenic conversion when compared with the effect of serum. This study presents results of first complex analysis of LAT from upper limb of breast cancer survivors. Identified LAT alterations indicate a possible link between (lymph)angiogenesis and lipolysis. In addition, our in vitro results imply that AT expansion in lymphedema could be driven partially by exposition of adipose precursors to undrained LAT-derived fluid.

Exercise Training Reduces Inflammation of Adipose Tissue in the Elderly: Cross-Sectional and Randomized Interventional Trial.

CONTEXT: Metabolic disturbances and a pro-inflammatory state associated with aging and obesity may be mitigated by physical activity or nutrition interventions. OBJECTIVE: The aim of this study is to assess whether physical fitness/exercise training (ET) alleviates inflammation in adipose tissue (AT), particularly in combination with omega-3 supplementation, and whether changes in AT induced by ET can contribute to an improvement of insulin sensitivity and metabolic health in the elderly. DESIGN, PARTICIPANTS, MAIN OUTCOME MEASURES: The effect of physical fitness was determined in cross-sectional comparison of physically active/physically fit (trained) and sedentary/less physically fit (untrained) older women (71 ± 4 years, n = 48); and in double-blind randomized intervention by 4 months of ET with or without omega-3 (Calanus oil) supplementation (n = 55). Physical fitness was evaluated by spiroergometry (maximum graded exercise test) and senior fitness tests. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Samples of subcutaneous AT were used to analyze mRNA gene expression, cytokine secretion, and immune cell populations. RESULTS: Trained women had lower mRNA levels of inflammation and oxidative stress markers, lower relative content of CD36+ macrophages, and higher relative content of γδT-cells in AT when compared with untrained women. Similar effects were recapitulated in response to a 4-month ET intervention. Content of CD36+ cells, γδT-cells, and mRNA expression of several inflammatory and oxidative stress markers correlated to insulin sensitivity and cardiorespiratory fitness. CONCLUSIONS: In older women, physical fitness is associated with less inflammation in AT. This may contribute to beneficial metabolic outcomes achieved by ET. When combined with ET, omega-3 supplementation had no additional beneficial effects on AT inflammatory characteristics.

Lymphatic drainage affects lipolytic activity of femoral adipose tissue in women.

It has been shown that many molecules released by adipose tissue (AT) into interstitial fluid can reach the bloodstream preferentially via lymphatic system. Worsened lymphatic drainage may alter interstitial fluid (ISF) composition and thus affect microenvironment of adipocytes. Nevertheless, the effect of lymphatic drainage on AT functions remains unknown. Therefore, we analyzed the lipolytic activity of femoral AT in two groups of premenopausal women similar in adiposity but differing in the efficiency of lymphatic drainage of lower body as assessed by lymphoscintigraphy. Levels of lipolytic markers were assessed in plasma and ISF collected by skin blister technique in femoral area. In addition, microdialysis was used to monitor lipolysis of AT in vivo. Our results indicate that worsened lymphatic drainage is associated with lower in vivo lipolytic index and reduced lipolytic responsiveness of femoral AT to adrenergic stimuli. Thus, efficiency of lymphatic drainage appears to play a role in the regulation of AT metabolism. Accordingly, worsened lymphatic drainage could contribute to the resistance of lower body AT to intentional weigh loss.