Catalpic acid decreases abdominal fat deposition, improves glucose homeostasis and upregulates PPAR α expression in adipose tissue (original) (raw)
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Lipids in health and disease, 2005
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-gamma (PPARgamma) 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 PPARgamma and PPARalpha reporter gene assays. Inclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lepob/lepob) 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 PPARgamma agonist rosig...
Journal of Nutritional Biochemistry, 2006
A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis 9, trans 11 ( c 9, t 11) and trans 10, cis 12 ( t 10, c 12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the t 10, c 12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t 10, c 12 CLA affects lipid accumulation in adipocytes. We have shown that t 10, c 12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 M and 25 M, respectively. t 10, c 12 CLA fails to activate peroxisome proliferator-activated receptor ␥ (PPAR ␥ ) but selectively inhibits thiazolidinedione-induced PPAR ␥ activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with t 10, c 12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPAR ␥ as well as its target genes, fatty acid binding protein (aP2) and liver X receptor ␣ (LXR ␣ ). Taken together, our results suggest that the trans 10, cis 12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPAR ␥ modulator. -Granlund, L., L. K. Juvet, J. I. Pedersen, and H. I. Nebb. Trans 10, cis 12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPAR ␥ modulator. J. Lipid Res. 2003. 44: 1441-1452.
Chemico-Biological Interactions, 2010
Excess visceral adiposity may predispose to chronic diseases like hypertension and type 2 diabetes with a high risk for coronary artery disease. Adipose tissue secreted cytokines and oxidative stress play an important role in chronic disease progression. To combat adiposity, plant-derived triterpenes are currently receiving much attention as they possess antioxidant and anti-inflammatory properties and the ability to regulate glucose and lipid metabolism. In the search for potential antiobese compounds from natural sources, this study evaluated the effects of oleanolic acid (OA), a pentacyclic triterpene commonly present in fruits and vegetables, in glucose tolerance test and on high-fat diet (HFD)-induced obesity in mice. Adult male Swiss mice treated or not with OA (10 mg/kg) were fed a HFD during 15 weeks. Sibutramine (SIB) treated group (10 mg/kg) was included for comparison. Weekly body weights, food and water consumption were measured, and at the end of study period, the levels of blood glucose and lipids, plasma hormone levels of insulin, ghrelin and leptin, and the visceral abdominal fat content were analysed. Mice treated with OA and fed a HFD showed significantly (p < 0.05) improved glucose tolerance, decreased body weights, visceral adiposity, blood glucose, plasma lipids relative to their respective controls fed no OA. Additionally, OA treatment, while significantly elevating the plasma hormone level of leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than lipase. Sibutramine-treated group also manifested similar effects like OA except for blood glucose level that was not different from HFD control. These findings suggest that OA ameliorates visceral adiposity and improves glucose tolerance in mice and thus has an antiobese potential through modulation of carbohydrate and fat metabolism.
The Journal of Lipid Research, 2003
A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis 9, trans 11 ( c 9, t 11) and trans 10, cis 12 ( t 10, c 12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the t 10, c 12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t 10, c 12 CLA affects lipid accumulation in adipocytes. We have shown that t 10, c 12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 M and 25 M, respectively. t 10, c 12 CLA fails to activate peroxisome proliferator-activated receptor ␥ (PPAR ␥ ) but selectively inhibits thiazolidinedione-induced PPAR ␥ activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with t 10, c 12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPAR ␥ as well as its target genes, fatty acid binding protein (aP2) and liver X receptor ␣ (LXR ␣ ). Taken together, our results suggest that the trans 10, cis 12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPAR ␥ modulator. -Granlund, L., L. K. Juvet, J. I. Pedersen, and H. I. Nebb. Trans 10, cis 12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPAR ␥ modulator. J. Lipid Res. 2003. 44: 1441-1452.
Journal of Lipid Research, 2003
A group of polyunsaturated fatty acids called conjugated linoleic acids (CLAs) are found in ruminant products, where the most common isomers are cis 9, trans 11 (c 9, t 11) and trans 10, cis 12 (t 10, c 12) CLA. A crude mixture of these isomers has been shown in animal studies to alter body composition by a reduction in body fat mass as well as an increase in lean body mass, with the t 10, c 12 isomer having the most pronounced effect. The objective of this study was to establish the molecular mechanisms by which t 10, c 12 CLA affects lipid accumulation in adipocytes. We have shown that t 10, c 12 CLA prevents lipid accumulation in human and mouse adipocytes at concentrations as low as 5 M and 25 M, respectively. t 10, c 12 CLA fails to activate peroxisome proliferator-activated receptor ␥ (PPAR ␥) but selectively inhibits thiazolidinedione-induced PPAR ␥ activation in 3T3-L1 adipocytes. Treatment of mature adipocytes with t 10, c 12 CLA alone or in combination with Darglitazone down-regulates the mRNA expression of PPAR ␥ as well as its target genes, fatty acid binding protein (aP2) and liver X receptor ␣ (LXR ␣). Taken together, our results suggest that the trans 10, cis 12 CLA isomer prevents lipid accumulation in adipocytes by acting as a PPAR ␥ modulator.-Granlund, L., L. K. Juvet, J. I. Pedersen, and H. I. Nebb. Trans 10, cis 12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPAR ␥ modulator.
Diabetes, 2001
studies with animal models. Previously, we reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and activated peroxisome proliferatoractivated receptor (PPAR)-␥ response elements in vitro. Here, our aim was to elucidate the effect(s) of specific CLA isomers on whole-body glucose tolerance, insulin action in skeletal muscle, and expression of genes important in glucose and lipid metabolism. ZDF rats were fed either a control diet (CON), one of two CLA supplemented diets (1.5% CLA) containing differing isoforms of CLA (47% c9,t11; 47.9% c10,t12, 50:50; or 91% c9,t11, c9,t11 isomers), or were pair-fed CON diet to match the intake of 50:50. The 50:50 diet reduced adiposity and improved glucose tolerance compared with all other ZDF treatments. Insulin-stimulated glucose transport and glycogen synthase activity in skeletal muscle were improved with 50:50 compared with all other treatments. Neither phosphatidlyinositol 3-kinase activity nor Akt activity in muscle was affected by treatment. Uncoupling protein 2 in muscle and adipose tissue was upregulated by c9,t11 and 50:50 compared with ZDF controls. PPAR-␥ mRNA was downregulated in liver of c9,t11 and pair-fed ZDF rats. Thus, the improved glucose tolerance in 50:50 rats is attributable to, at least in part, improved insulin action in muscle, and CLA effects cannot be explained simply by reduced food intake.
British Journal of Nutrition, 2009
Conjugated linoleic acid (CLA) isomers have been reported to reduce body weight and beneficially affect glucose metabolism in animals, but the results are inconsistent and seem to depend on animal model and type of CLA isomer. In the present study, feeding male Zucker fa/fa rats diets supplemented with 1 % trans-10, cis-12-CLA for 10 d reduced the liver TAG content without improving the overall adiposity, and enhanced hepatic mitochondrial and peroxisomal b-oxidation. The increased carnitine palmitoyltransferase (CPT)-I activity and mRNA level as well as the increased n-3:n-6 PUFA ratio in liver suggest that trans-10, cis-12-CLA increased the hepatic b-oxidation by stimulation of PPARa. The reduced hepatic TAG content may be partly due to lower activity of stearoyl-CoA desaturase, as the ratios of 18 : 1n-9:18 : 0 and 16 : 1n-7:16 : 0 were reduced in liver. Trans-10, cis-12-CLA increased the CPT-I mRNA in retroperitoneal white adipose tissue (WAT), and increased uncoupling protein-2 mRNA in epididymal and inguinal WAT depots. Leptin mRNA level was decreased in all examined WAT depots, implying reduced insulin sensitivity. The resistin mRNA level was increased in all WAT depots, whereas adiponectin mRNA was reduced in inguinal and retroperitoneal WAT. The present results suggest that dietary supplementation with trans-10, cis-12-CLA may increase the catabolism of lipids in liver and adipose tissue. Moreover, we provide new data suggesting that trans-10, cis-12-CLA modulates the expression of resistin and adiponectin inversely in adipose tissue. Hence, the present results suggest that trans-10, cis-12-CLA may have some beneficial effects on lipid metabolism and adiposity but possibly reduces insulin sensitivity.
Metabolism, 2007
Conjugated linoleic acids (CLA) have been shown to alter adiposity in some species with varying effects on insulin resistance. The objective of this 8-week study was to investigate the effects of feeding a CLA mixture (1.5%, wt/wt) on adipocyte size, insulin sensitivity, adipokine status, and adipose lipid composition in fa/fa vs lean Zucker rats. The fa/fa CLA-fed rats had smaller adipocytes and improved insulin sensitivity compared with fa/fa rats fed the control diet. Conjugated linoleic acids did not affect select markers of adipose differentiation, lipid filling, lipid uptake, or oxidation. Dietary CLA, compared with the control diet, reduced circulating leptin and elevated fasting serum adiponectin concentrations in fa/fa rats. Adipose resistin messenger RNA levels were greater in fa/fa CLA-fed rats compared with fa/fa control rats. CLA did not markedly alter adipose phospholipid fatty acid composition, and the changes in the triacylglycerol fatty acid composition reflected a lower delta-9 desaturase index of CLA-fed vs control-fed rats. In conclusion, CLA reduced adipocyte size and favorably modified adipokine status and insulin sensitivity in fa/fa Zucker rats.
Journal of Ethnopharmacology, 2020
Khat (Catha edulis (Vahl) Forssk.) is a herb from the Celastraceae family (also known as qat, gaad, or mirra) that is widely-consumed in East Africa and in the Arabian peninsula. The green leaves and small stems are consumed primarily at recreational and social gatherings, and medicinally for their antidiabetic and appetite-suppression effects. Aims: The objectives of this study were to determine the effects of khat and its active alkaloid, cathinone, on food intake and body weight in mice maintained on a high-fat diet, and to investigate its mechanism of action in white adipose tissue and in the hypothalamus. Materials & Method: Adult male mice (C57BL/6J) were fed a high fat diet (HFD) for 8 weeks (n ¼ 30), then divided into 5 groups and treated daily for a further 8 weeks with HFD þ vehicle [control (HFD)], HFD þ 15 mg/ kg orlistat (HFDO), HFD þ 200 mg/kg khat extract (HFDK200), HFD þ 400 mg/kg khat extract (HFDK400) and HFD þ 3.2 mg/kg cathinone (HFDCAT). Treatments were carried out once daily by gastric gavage. Blood and tissue samples were collected for biochemical, hormonal and gene expression analyses. Results: Khat extracts and orlistat treatment significantly reduced weight gain as compared to control mice on HFD, and cathinone administration completely prevented weight gain in mice fed on HFD. Khat treatment caused a marked reduction in body fat and in serum triglycerides. A dose-dependent effect of khat was observed in reducing serum leptin concentrations. Analysis of gene expression in adipose tissue revealed a significant upregulation of two lipolysis pathway genes:(adipose triglyceride lipase (PNPLA-2) and hormone-sensitive lipase (LIPE). In the hypothalamic there was a significant (P < 0.05) upregulation of agouti-related peptide (AgRP) and cocaine-amphetamine regulated transcript (CART) genes in the HFDK400 and HFDCAT groups. Conclusion: Cathinone treatment blocked body weight gain, while high dose khat extract significantly reduced the weight gain of mice on an obesogenic diet through stimulation of lipolysis in white adipose tissue.