Cholecystokinin (CCK) decreases meal size through activation of CCK-A receptors on vagal afferents. We tested the hypothesis that the selective CCK-A agonist GI181771X induces weight loss in obese patients. Patients with body mass index > or = 30 or > or = 27 kg/m2 with concomitant risk factors were randomized to 24-week, double-blind treatment with different GI181771X doses or matching placebo together with a hypocaloric diet. The primary efficacy end point was the absolute change in body weight. To monitor pancreatic and gallbladder effects, patients underwent abdominal ultrasound and magnetic resonance imaging before and after treatment. We randomized 701 patients to double-blind treatment. GI181771X did not reduce body weight and had no effect on waist circumference or other cardiometabolic risk markers. Gastrointestinal side effects were more common with GI181771X than with placebo treatment, whereas hepatobiliary or pancreatic abnormalities did not occur. CCK-A by itself does not have a central role in long-term energy balance.
Objectives: To evaluate the feasibility and long-term compliance with a low-fat diet supplemented with soy protein in men at increased risk for recurrence after radical prostatectomy. Design: Randomized, control study. Setting: Academic center in USA. Subject: Forty men who had undergone radical prostatectomy and were at increased risk for recurrence. Intervention: Low-fat (15% fat), high-fiber (18 g/1000 kcal) diet supplemented with 40 g soy protein isolate (n ¼ 26) was compared to USDA recommended diet (n ¼ 14). Results: Over 4 years, subjects in the intervention group but not in the control group made and sustained significant changes in their diet as measured by the dietary assessment instruments and urinary isoflavone excretion. In the intervention group, dietary fat intake was reduced from 33.4671.27% energy/day to 21.0471.74% (Po0.05), fiber intake increased from 14.671.06 to 21.0572.29 g/day. The insulin growth factor-1 (IGF-1) level was decreased from 260.478.6 ng/ml at baseline to 220.577.9 ng/ml at 6 months (Po0.05) in the intervention group with no significant change in the control group. An ex vivo assay demonstrated inhibition of LNCaP cell growth (À20.077.7%, Po0.05) by sera from patients in the intervention group after 6 months of dietary change compared to baseline. Conclusion: These data suggest that long-term low-fat dietary interventions as part of prospective randomized trials in prostate cancer survivors are feasible, and lead to reductions in circulating hormones or other growth factors stimulating prostate cancer growth ex vivo.
Background and ObjectivesObesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.Materials and MethodsMale C57BL/6J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes, and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic, and Type II diabetic patients were measured by ELISA.ResultsLentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared to non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.ConclusionsCathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.
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