Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation

BACKGROUND: Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-γ (PPARγ) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARγ and PPARα reporter gene assays. RESULTS: Inclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lep(ob)/lep(ob)) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARγ agonist rosiglitazone, CLA or CLA enriched with its trans-10, cis-12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFα concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans-10, cis-12 isomer, but not with its cis-9, trans-11 isomer, stimulated PPARγ-mediated reporter gene activity; both isomers stimulated PPARα-mediated reporter gene activity. CONCLUSIONS: CLA initially decreased but subsequently increased insulin sensitivity in lep(ob)/lep(ob )mice. Activation of both PPARγ and PPARα may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans-10, cis-12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity

Team librarianship in public libraries: an assessment of the new tradition in structural organization

Team librarianship in public libraries: an assessment of the new tradition in structural organizatio

Case study of the electrical hardware and software for a flowmeter calibration facility

In the development of a flow test rig as a tool for investigating manufacturing variation and providing guidance to manufacturers considering setting up such a rig for calibration of meters at the end of the production line, we encountered various problems. We discussed some of these in a previous paper in Baker et al. (2006). [1]. In a subsequent paper in Shimada et al. (2010). [2] we reported on tests aimed at identifying the limits of measurement trueness of the rig and the obtainable precision (VIM (1993); Amended 1995 Supplements (1993). [3,4]) with this type of design. In this paper we discuss the aims for signal measurement and the design, implementation of hardware and software, and the commissioning of the system. In particular, we have set out in some detail the problems encountered which we suspect are experienced by others, and the solutions found which appear to be justified by their application to a rebuilt rig with satisfactory performance. © 2012 Elsevier Ltd

The Effects of Ppar Delta and Alpha Agonist on Fatty Acid and Glucose Metabolism in Vivo and in Mouse Isolated Soleus Muscle

The peroxisome proliferator-activated receptors of the nuclear receptor superfamily are het-erodimers with the 9-cis retinoic acid receptor and bind to specific peroxisome proliferators re-sponse elements to regulate the transcription of their target genes resulting in the regulation of lipid, metabolism, glucose homeostasis and inflammation. Activation of these receptors by their agonists has since been shown to play critical and unique roles in lipid homeostasis. This work was designed to study the effects of PPAR-õ agonists and PPAR-α agonist on lipid and glucose homeostasis in models of diabetes and obesity in C57B1/6 mice. The effect of PPAR-õ agonist, GW610742, and PPAR-α agonist GW649003 on lipid and glucose metabolism were studied in C57B1/6 lean and obese mice. GW610742 was administered, p.o at 3mg/kg body weight and 10mg/kg body weight at 09.00h and 17.00h in two separate groups of lean mice in an acute study. The dosing was repeated over seven days in another two groups of mice in the chronic study. C57B1/6 obese and lean mice were also dosed with GW800644 (10mg/kg) and GW649003 (1mg/kg) p.o at 09.00h and 17.00h for 14 days. At the end of study, glucose, lactate, and NEFA were measured. Animals were killed; whole organs were removed and weighed. The soleus mus-cles were isolated and used to determine 2-deoxyglucose uptake and palmitate oxidation. GW610742 did not show any significant metabolic changes in lean mice in both the acute and chronic studies. However, chronic treatment with GW800644 and GW649003 in ob/ob mice, resulted in an increase uptake of 2-deoxyglucose and palmitate oxidation in mouse isolated so-leus muscle and decreased plasma glucose and insulin levels. However, GW649003 also induced hepatomegaly in lean mice but not in the obese. The fact that both PPAR-δ agonist GW800644 and PPAR-α agonist GW649003 showed a positive lipid, glucose and insulin homeostasis only in mice with these metabolic defects shows they have the potentials to be developed into drugs for management of diabetes and obesity