Development Of Related Metabolic Disorders Research Articles

Tunicamycin-Induced Endoplasmic Reticulum Stress Mediates Mitochondrial Dysfunction in Human Adipocytes.

Dysfunctional endoplasmic reticulum (ER) and mitochondria are known to contribute to the pathology of metabolic disease. This damage may occur, in part, as a consequence of ER-mitochondria cross-talk in conditions of nutrient excess such as obesity. To date, insight into this dynamic relationship has not been characterized in adipose tissue. Therefore, this study investigated whether ER stress contributes to the development of mitochondrial inefficiency in human adipocytes from lean and obese participants. Human differentiated adipocytes from Chub-S7 cell line and primary abdominal subcutaneous adipocytes from lean and obese participants were treated with tunicamycin to induce ER stress. Key parameters of mitochondrial function were assessed, including mitochondrial respiration, membrane potential (MMP), and dynamics. ER stress led to increased respiratory capacity in a model adipocyte system (Chub-S7 adipocytes) in a concentration and time dependent manner (24 h: 23%↑; 48 h: 68%↑, P < 0.001; 72 h: 136%↑, P < 0.001). This corresponded with mitochondrial inefficiency and diminished MMP, highlighting the formation of dysfunctional mitochondria. Morphological analysis revealed reorganization of mitochondrial network, specifically mitochondrial fragmentation. Furthermore, p-DRP1, a key protein in fission, significantly increased (P < 0.001). Additionally, adipocytes from obese subjects displayed lower basal respiration (49%↓, P < 0.01) and were unresponsive to tunicamycin in contrast to their lean counterparts, demonstrating inefficient mitochondrial oxidative capacity. These human data suggest that adipocyte mitochondrial inefficiency is driven by ER stress and exacerbated in obesity. Nutrient excess-induced ER stress leads to mitochondrial dysfunction that may therefore shift lipid deposition ectopically and thus have further implications on the development of related metabolic disorders.

Influence of insulin resistance on renal function in patients with abdominal obesity.

The purpose of the study - to assess the role of insulin resistance in the development of initial manifestations of renal disease in patients with abdominal obesity. Materials and methods – 61 patients (I group) young with obesity, I-III degree, without diabetes 1 or type 2 were examined. The structure of the control group included 12 patients who were considered to be relatively healthy (II group), 10 patients with newly diagnosed type 2 diabetes (III group) and 10 individuals with uncomplicated hypertension without abdominal obesity and diabetes. The effect of hyperinsulinemia and insulin resistance indices on renal function (glomerular filtration rate, urine protein, urine albumin, urine β 2 -microglobulin, and relations - urine albumin / creatinine urine, β 2 -microglobulin urine/urine creatine) was studied. Results and discussion. Main group of patients, group of patients with diabetes type 2 and uncomplicated hypertension is characterized by disturbances in the form of hyperinsulinemia and increased insulin resistance index. Statistical analysis showed significant relationships between indicators of fasting insulin, IR index and renal function in patients with abdominal obesity. Regression analysis confirmed the pattern between the level of insulin resistance and the main indicators of renal function (GFR, MAU, β 2 -microglobulinuria and increased ratio β2-microglobulin/urine creatinine). Conclusions. In patients with abdominal obesity disorders in the form of hyperinsulinemia and increased insulin resistance index of HOMA-IR>2,77 were revealed. Significant correlation connections between levels of fasting insulin, insulin resistance index and indicators of renal function were observed. In regression analysis predictive role of insulin resistance in the formation of renal dysfunction in patients with abdominal obesity was established. The necessity of studying the state of insulin resistance in patients with obesity-associated nephropathy for the selection of adequate pathogenetic therapy, prognosis of renal dysfunction and prevention of the development of related metabolic disorders.

Training induced changes in the fatty acid composition of skeletal muscle lipids. Functional aspects.

Insulin sensitivity relates to the fatty acid composition of the skeletal muscle phospholipids and the intramuscular triglyceride content. The fatty acid composition of the phospholipids--but not of the triglycerides--in the muscles are influenced by regular physical activity of low-moderate intensity. An increased degree of unsaturation of the cell membranes after training may hypothetically contribute to the improvement of insulin sensitivity. Different ways of reducing the supply of lipids in the muscles may possibly cause similar changes of the fatty acid composition of the cell membranes. Further studies are needed to explore the relationships between changes of the skeletal muscle lipid composition during physical activity, the interaction with dietary fat intake, and changes of insulin sensitivity and development of related metabolic disorders.