INTRODUCTION: Cardiac cachexia is a catabolic state in which adipose tissue atrophy is accompanied by a proinflammatory state. The molecular mechanisms underlying proinflammatory activation remain, however, largely unknown. In this experimental study, the effect of a high-calorie diet was analyzed in the advanced stages of monocrotaline-induced pulmonary hypertension (PH). METHODS: Male Wistar rats (180-200 g; n=28) were randomly injected with either monocrotaline (MCT; 60 mg/kg; sc) or vehicle. Each group was then assigned to either a regular diet (2.9 kcal/g) or a high-calorie diet with a high fat and simple carbohydrate content (5.4 kcal/g). Twenty-four to 32 days after injection, adipose tissue was collected for morphometric, histological and molecular analysis. The proportional weight of the gonadal fat pad was used as an adiposity index. Detection of macrophages in adipose tissue was performed with an anti-CD6 monoclonal antibody. Interleukin-6 (IL-6) mRNA quantification was performed using real-time RT-PCR. RESULTS: MCT injection was accompanied by a reduction in adiposity (-51 +/- 3.4%) and by adipocyte atrophy (-18 +/- 1.4%). This was accompanied by IL-6 overexpression (+879 +/- 444%), but there were no changes in adipose tissue macrophage content. Exposure to a high-calorie diet in the MCT group attenuated adipose tissue atrophy as well as IL-6 gene overexpression. CONCLUSION: A high-calorie diet attenuates cachexia and proinflammatory activation in the advanced stages of monocrotaline-induced PH. These results suggest nutritional state potential therapeutic target in advanced PH
INTRODUCTION:Cardiac cachexia is a catabolic state in which adipose tissue atrophy is accompanied by a proinflammatory state. The molecular mechanisms underlying proinflammatory activation remain, however, largely unknown. In this experimental study, the effect of a high-calorie diet was analyzed in the advanced stages of monocrotaline-induced pulmonary hypertension (PH). METHODS: Male Wistar rats (180-200 g; n=28) were randomly injected with either monocrotaline (MCT; 60 mg/kg; sc) or vehicle. Each group was then assigned to either a regular diet (2.9 kcal/g) or a high-calorie diet with a high fat and simple carbohydrate content (5.4 kcal/g). Twenty-four to 32 days after injection, adipose tissue was collected for morphometric, histological and molecular analysis. The proportional weight of the gonadal fat pad was used as an adiposity index. Detection of macrophages in adipose tissue was performed with an anti-CD6 monoclonal antibody. Interleukin-6 (IL-6) mRNA quantification was performed using real-time RT-PCR. RESULTS:MCT injection was accompanied by a reduction in adiposity (-51 +/- 3.4%) and by adipocyte atrophy (-18 +/- 1.4%). This was accompanied by IL-6 overexpression (+879 +/- 444%), but there were no changes in adipose tissue macrophage content. Exposure to a high-calorie diet in the MCT group attenuated adipose tissue atrophy as well as IL-6 gene overexpression. CONCLUSION: A high-calorie diet attenuates cachexia and proinflammatory activation in the advanced stages of monocrotaline-induced PH. These results suggest nutritional state potential therapeutic target in advanced PH