Skeletal muscle expression of adipose-specific phospholipase in peripheral artery disease.

Flow-limiting atherosclerotic lesions of arteries supplying the limbs are a cause of symptoms in patients with peripheral artery disease (PAD). Musculoskeletal metabolic factors also contribute to the pathophysiology of claudication, which is manifest as leg discomfort that impairs walking capacity. Accordingly, we conducted a case-control study to determine whether skeletal muscle metabolic gene expression is altered in PAD. Calf skeletal muscle gene expression of patients with PAD and healthy subjects was analyzed using microarrays. The top-ranking gene differentially expressed between PAD and controls (FDR < 0.001) was PLA2G16, which encodes adipose-specific phospholipase A2 (AdPLA) and is implicated in the maintenance of insulin sensitivity and regulation of lipid metabolism. Differential expression was confirmed by qRT-PCR; PLA2G16 was downregulated by 68% in patients with PAD (p < 0.001). Expression of Pla2g16 was then measured in control (db/+) and diabetic (db/db) mice that underwent unilateral femoral artery ligation. There was significantly reduced expression of Pla2g16 in the ischemic leg of both control and diabetic mice (by 51%), with significantly greater magnitude of reduction in the diabetic mice (by 79%). We conclude that AdPLA is downregulated in humans with PAD and in mice with hindlimb ischemia. Reduced AdPLA may contribute to impaired walking capacity in patients with PAD via its effects on skeletal muscle metabolism. Further studies are needed to fully characterize the role of AdPLA in PAD and to investigate its potential as a therapeutic target for alleviating symptoms of claudication.

Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

OBJECTIVE: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. METHODS: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. RESULTS: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. CONCLUSIONS: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

Uma experiência multiprofissional na abordagem ao paciente hipertenso / An Interdistiplinarian Experience on Approaching Patients with Hypertension

Objetivo - Estudar o impacto das atividades educativas na abordagem ao paciente hipertenso, com equipe multiprofissional, num período mínimo de 5 e máximo de 9 meses, em aspectos relacionados à hipertensão arterial (HA). Métodos - Cinqüenta indivíduos constituindo dois grupos de 25 cada. O grupo A formado de pacientes que participavam das atividades educativas da Liga de Hipertensão Arterial (LHA) e o grupo B. também de pessoas matriculadas na LHA, mas não participantes. Os grupos eram comparáveis no tocante à idade, sexo, tipo e duração do tratamento. Foram estudados os grupos com relação à pressão arterial (PA), peso, tabagismo, ingestão alcoólica, exercícios físicos e freqüência às consultas. Resultados - Houve queda da PA em 84% dos pacientes do grupo A e 88% do grupo B. redução de peso em 60% do grupo A e 44% do grupo B e a prática de exercícios físicos foi hábito regular em 56% do grupo A e 36% do grupo B. No grupo A foi encontrado 4% de tabagistas e no grupo B 16%. A ingestão alcoólica esteve presente em 12% do grupo A e 24% do grupo B. Os pacientes do grupo A faltaram menos às consultas (30%) do que os do grupo B (44%). Conclusão - Apesar de não observarmos diferenças significativas entre as duas formas de abordagem, no que diz respeito ao controle da PA, observamos nítida vantagem a favor de uma abordagem educativa em grupo, com participação de equipe multiprofissional

Purpose - To evalvate the impact of the educational approach of activities on the approach of patients with hypertension, with an interdisciplinarian team. Methods - Fifty patients divided into two groups: A) with 25 patients who participated in educational activities in the Hipertension League (HL) and B) who were also registered and did not take part in the activities. They were studied regarding blood pressure (BP), weight control, smoking habits, alcoholic beverage consumption, physical activities and frequency of medical care. Results - There was a drop in BP of 84% of the patients in group A and 88% in group B. a drop in weight in 60% of group A and 44% of group B. We registered the presence of 4% of smokers in group A and 16% in group B. Physical activities were regular in 56% of group A and 36% in group B. Absenteeism to meetings was slighty higher among group B (44°/0) when compared with group A (30°/0). Conclusion - In spite of not having observed any significant differences between both approaches, regarding to strict BP control, we were able to observe a noticeable advantage in favor of the educational approach to the group, with participation of interdisciplinarian team