—Kidney failure is the common end of hypertension and renal diseases. Several authors have suggested that vasodilatory prostaglandins participate in the hemodynamic mechanism responsible for the development of kidney failure. However, the mechanism by which prostaglandins are increased in renal disease is not clear. Recently, 2 isoforms of the enzyme responsible for prostaglandin synthesis, cyclooxygenase, have been described as cyclooxygenase-1 (COX-1), a constitutive isoform, and cyclooxygenase-2 (COX-2), an inducible isoform. In the present study, we investigated whether COX-2–dependent prostaglandins participate in the evolution of renal functional changes after renal ablation. We inhibited prostaglandin synthesis by COX-1 and COX-2 with indomethacin (3 mg/kg) and prostaglandin synthesis by COX-2 with NS-398 (3 mg/kg) and tested the effect of these inhibitors on the renal functional changes elicited by renal ablation. Renal ablation produced an increase in urinary volume, protein, and prostaglandin E ₂ , whereas urinary sodium and potassium were not affected and urinary osmolarity decreased; treatment with indomethacin or NS-398 partially prevented the renal functional changes elicited by renal ablation. Immunoblots for COX showed an increase in the expression of COX-2 protein 2 days after renal ablation. Furthermore, COX-2 mRNA expression was increased 1 day after renal ablation. These data suggest that COX-2–dependent prostaglandins participate in the renal mechanisms associated with the development of renal functional changes after renal ablation.

OBJECTIVE: Type 2 diabetes is the most common form of diabetes worldwide. Some of its complications, such as retinopathy and neuropathy, are long-term and protracted, with an unclear etiology. Given this problem, genetic model systems, such as in flies where type 2 diabetes can be modeled and studied, offer distinct advantages. RESEARCH DESIGN AND METHODS: We used individual flies in experiments: control and mutant individuals with partial loss-of-function insulin pathway genes. We measured wing size and tested body weight for growth phenotypes, the latter by means of a microbalance. We studied total lipid and carbohydrate content, lipids by a reaction in single fly homogenates with vanillin-phosphoric acid, and carbohydrates with an anthrone-sulfuric acid reaction. Cholinesterase activity was measured using the Ellman method in head homogenates from pooled fly heads, and electroretinograms with glass capillary microelectrodes to assess performance of central brain activity and retinal function. RESULTS: Flies with partial loss-of-function of insulin pathway genes have significantly reduced body weight, higher total lipid content, and sometimes elevated carbohydrate levels. Brain function is impaired, as is retinal function, but no clear correlation can be drawn from nervous system function and metabolic state. CONCLUSIONS: These studies show that flies can be models of type 2 diabetes. They weigh less but have significant lipid gains (obese); some also have carbohydrate gains and compromised brain and retinal functions. This is significant because flies have an open circulatory system without microvasculature and can be studied without the complications of vascular defects.

A high saturated fat and fructose diet leads to metabolic disorders through dysregulation of genes involved in lipid metabolism. Consumption of plant infusions reduces these obesity alterations, but the precise mechanism remains unclear. In this study, we investigated the effect and the possible mechanism of Ocimum sanctum L. (OS) and Citrus paradisi (CP) infusions in diet-induced obese rats. CP and OS infusions suppressed hepatic tissue fat accumulation, and significantly down-regulated the mRNA levels of two hepatic lipogenesis genes: sterol regulatory element binding protein 1c (SREBP1c) and fatty acid synthase (FAS) compared with the obese control. Treatment with these infusions up-regulated the hepatic expression of mRNA related to mitochondrial fatty acid uptake: peroxisome proliferator activated receptor alpha (PPARα) and the expression of carnitine palmitoyl-transferase 1a (CPT1a). Both infusions improved insulin resistance, with OS showing the major effect. Consumption of these infusions reduces the damage caused by free radicals, protecting hepatic lipids and proteins. Additionally, plant infusions increase activity of hepatic enzymes: glutathione S-transferase (GST), glutathione peroxidase (GPX), and catalase (CAT). Our results suggest that the effects of CP and OS infusions on lipid metabolism are related to the down-regulation of genes involved in lipogenesis, particularly for OS, and to the increase in lipid β-oxidation, especially for CP infusion. In conclusion, the consumption of these plant infusions is a feasible adjuvant therapy for metabolic changes induced by obesity.