Effects of homocysteine on adipocyte differentiation and CD36 gene expression in 3T3-L1 adipocytes

The aim of this study was to investigate the effects of homocysteine (Hcy), a risk factor for cardiovascular diseases, hypertension, stroke and obesity, on expression of CD36 that regulates uptake of oxidized low-density lipoprotein (Ox-LDL) by adipocytes and differentiation of 3T3-L1 cells to adipocytes. Cell viability was determined using MTT assay, and density of triglycerides were measured with Oil Red O staining. The expression levels of CD36 were analyzed using SYBR green assay by quantitative RT-PCR. Our results showed that the addition of Hcy inhibited differentiation of 3T3-L1 preadipocytes in a dose-dependent manner without a significant cell toxicity (p < 0.05). Percentage CD36 gene expression increased in the Hcy treatment groups, but not statistically significantly (p > 0.05) compared to differentiated adipocytes. Hcy reduced adipocyte differentiation, but had no effect on the expression level of CD36 in vitro conditions. The effect of Hcy on uptake and clearance of Ox-LDL by adipose tissue now needs to be investigated in vivo

PPAR alpha: an emerging therapeutic target in diabetic microvascular damage

The global pandemic of diabetes mellitus portends an alarming rise in the prevalence of microvascular complications, despite advanced therapies for hyperglycemia, hypertension and dyslipidemia. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is expressed in organs affected by diabetic microvascular disease (retina, kidney and nerves), and its expression is regulated specifically in these tissues. Experimental evidence suggests that PPAR alpha activation attenuates or inhibits several mediators of vascular damage, including lipotoxicity, inflammation, reactive oxygen species generation, endothelial dysfunction, angiogenesis and thrombosis, and thus might influence intracellular signaling pathways that lead to microvascular complications. PPAR alpha has emerged as a novel target to prevent microvascular disease, via both its lipid-related and lipid-unrelated actions. Despite strong experimental evidence of the potential benefits of PPAR alpha agonists in the prevention of vascular damage, the evidence from clinical studies in patients with diabetes mellitus remains limited. Promising findings from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study on microvascular outcomes are countered by elevations in participants' homocysteine and creatinine levels that might potentially attenuate the benefits of PPAR alpha activation. This Review focuses on the role of PPAR alpha activation in diabetic microvascular disease and highlights the available experimental and clinical evidence from studies of PPAR alpha agonists