Pan-PPAR agonist beneficial effects in overweight mice fed a high-fat high-sucrose diet

Fernandes-Santos, Caroline; Carneiro, Rafael Evangelista; Mendonça, Leonardo de Souza; Águila, Márcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

doi:10.1016/j.nut.2008.12.010

Cited by 60 publications

(48 citation statements)

References 60 publications

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“…Thus, BVC exhibits differential effects on the expression of PPAR target genes involved in fatty acid metabolism, cholesterol metabolism and glucose transport. As a result, BVC decreases TG and LDL-C levels in both mouse models, but RSG exhibits the discrepancies in lipid regulation, which are also probably linked to species-specific regulation of VLDL and LDL particle size and concentration, and apolipoprotein [47][48][49]. Compared with the only clinical pan-PPAR agonist bezafibrate, BVC exhibited a stronger glucose-lowering effect [17].…”

Section: Discussionmentioning

confidence: 97%

Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-γ and PPAR-α agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice

Luo

et al. 2016

Diabetologia

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Section: Discussionmentioning

confidence: 97%

Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-γ and PPAR-α agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice

Luo

et al. 2016

Diabetologia

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“…Indeed, dysregulation of metabolism, such as insulin resistance and type 2 diabetes, is closely linked to the development of NASH. In the HF/HS model, fenofibrate (PPARα) is reported to prevent body and fat mass increase and fasting insulin increase but does not improve fasting glucose or glucose tolerance, while rosiglitazone (PPARγ) further increases body and fat mass versus diet‐control animals and in contrast to fenofibrate restores glucose tolerance and decreases fasting glucose and insulin levels 42. IVA337 almost normalized all these parameters; it also decreased plasma triglycerides and increased β oxidation.…”

Section: Discussionmentioning

confidence: 99%

The new‐generation pan‐peroxisome proliferator‐activated receptor agonist IVA337 protects the liver from metabolic disorders and fibrosis

Wettstein

Luccarini

Poekes

et al. 2017

Hepatology Communications

115

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IVA337 is a pan‐peroxisome proliferator‐activated receptor (PPAR) agonist with moderate and well‐balanced activity on the three PPAR isoforms (α, γ, δ). PPARs are regulators of lipid metabolism, inflammation, insulin resistance, and fibrogenesis. Different single or dual PPAR agonists have been investigated for their therapeutic potential in nonalcoholic steatohepatitis (NASH), a chronic liver condition in which steatosis coexists with necroinflammation, potentially leading to liver fibrosis and cirrhosis. Clinical results have demonstrated variable improvements of histologically assessed hepatic lesions depending on the profile of the tested drug, suggesting that concomitant activation of the three PPAR isoforms would translate into a more substantial therapeutic outcome in patients with NASH. We investigated the effects of IVA337 on several preclinical models reproducing the main metabolic and hepatic features associated with NASH. These models comprised a diet‐induced obesity model (high‐fat/high‐sucrose diet); a methionine‐ and choline‐deficient diet; the foz/foz model; the CCl4‐induced liver fibrosis model (prophylactic and therapeutic) and human primary hepatic stellate cells. IVA337 normalized insulin sensitivity while controlling body weight gain, adiposity index, and serum triglyceride increases; it decreased liver steatosis, inflammation, and ballooning. IVA337 demonstrated preventive and curative effects on fibrosis in the CCl4 model and inhibited proliferation and activation of human hepatic stellate cells, the key cells driving liver fibrogenesis in NASH. Moreover, IVA337 inhibited the expression of (pro)fibrotic and inflammasome genes while increasing the expression of β‐oxidation‐related and fatty acid desaturation‐related genes in both the methionine‐ and choline‐deficient diet and the foz/foz model. For all models, IVA337 displayed an antifibrotic efficacy superior to selective PPARα, PPARδ, or PPARγ agonists. Conclusion: The therapeutic potential of IVA337 for the treatment of patients with NASH is supported by our data. (Hepatology Communications 2017;1:524–537)

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“…The high-fat and high-sucrose (HFS) diet was based on AIN-93G 15) and used to induce obesity in the short term. 16) The HFS diet contained, on an energy basis, 32% carbohydrate including sucrose, 20% protein, and 48% fat. The increased lipid (lard) and sucrose was subtracted from -corn starch in the basal diet.…”

Section: Methodsmentioning

confidence: 99%

TRPV1 Agonist Monoacylglycerol Increases UCP1 Content in Brown Adipose Tissue and Suppresses Accumulation of Visceral Fat in Mice Fed a High-Fat and High-Sucrose Diet

Iwasaki

Tamura

Inayoshi

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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The administration of such a transient receptor potential vanilloid 1 (TRPV1) agonist as capsaicin, which is a pungent ingredient of red pepper, promotes energy metabolism and suppresses visceral fat accumulation. We have recently identified monoacylglycerols (MGs) having an unsaturated long-chain fatty acid as the novel TRPV1 agonist in foods. We investigated in this present study the effects of dietary MGs on uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT) and on fat accumulation in mice fed with a high-fat, high-sucrose diet. The MG30 diet that substituted 30% of all lipids for MGs (a mixture of 1-oleoylglycerol, 1-linoleoylglycerol and 1-linolenoylglycerol) significantly increased the UCP1 content of IBAT and decreased the weight of epididymal white adipose tissue, and the serum glucose, total cholesterol and free fatty acid levels. The diet containing only 1-oleoylglycerol as MG also increased UCP1 expression in IBAT. MGs that activated TRPV1 also therefore induced the expression of UCP 1 and prevented visceral fat accumulation as well as capsaicin.Key words: monoacylglycerol; transient receptor potential vaniloid 1 (TRPV1); uncoupling protein 1; obesity; capsaicin Obesity is a risk factor for hyperglycemia, hyperlipidemia and hypertension. It is important for preventing obesity to decrease the energy intake and increase the energy expenditure. It has been reported that capsaicin (CAP), a pungent ingredient of red pepper, is the functional ingredient for increasing energy expenditure. CAP promotes energy metabolism (oxygen consumption) by increasing adrenaline secreted from the adrenal medulla and upregulating uncoupling protein 1 (UCP1) in interscapular brown adipose tissue (IBAT) by activating the sympathetic nerve. 1-4) Since CAP has the effect of increasing energy expenditure, the ingestion of CAP could suppress the accumulation of visceral fat in rats fed with a high-fat diet. 5) The CAP receptor was identified as vanilloid receptor subtype 1 in 1997, 6) and has recently been called transient receptor potential vanilloid 1 (TRPV1). TRPV1 is mainly expressed in the primary afferent nerve. 6) Recent studies have indicated that stimulating the sensory nerve by activating TRPV1 was essential to CAP-induced energy expenditure. CAP-induced adrenaline secretion was completely dissipated in rats in which the CAP-sensitive sensory nerve had been denervated by an excess CAP treatment, 7) suggesting that the TRPV1-expressing sensory nerve was indispensable for CAPinduced adrenaline secretion. The effects of suppressing an accumulation of visceral fat, increasing oxygen consumption and promoting thermogenesis by CAP were canceled in TRPV1 knockout mice. 8,9) We searched in our previous study for the food compound which would activate TRPV1 as the functional compound increasing energy expenditure, and identified 1-or 2-monoacylglycerols (MGs) having oleic, linoleic, and -linolenic acids from wheat flour, onion (Allium cepa) and myoga (Zingiber mioga) as TRPV1 agonists. 10) The po...

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Pan-PPAR agonist beneficial effects in overweight mice fed a high-fat high-sucrose diet

Cited by 60 publications

References 60 publications

Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-γ and PPAR-α agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice

Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-γ and PPAR-α agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice

The new‐generation pan‐peroxisome proliferator‐activated receptor agonist IVA337 protects the liver from metabolic disorders and fibrosis

TRPV1 Agonist Monoacylglycerol Increases UCP1 Content in Brown Adipose Tissue and Suppresses Accumulation of Visceral Fat in Mice Fed a High-Fat and High-Sucrose Diet

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