Identification of a novel agonist of peroxisome proliferator-activated receptors α and γ that may contribute to the anti-diabetic activity of guggulipid in Lepob/Lepob mice

Cornick, Claire; Strongitharm, Barbara H.; Sassano, Gary; Rawlins, Christopher; Mayes, Andrew E.; Joseph, Alison N.; O’Dowd, Jacqueline; Stocker, Claire J.; Wargent, Edward T.; Cawthorne, Michael A.; Brown, Angela L.; Arch, Jonathan R. S.

doi:10.1016/j.jnutbio.2008.07.010

Cited by 22 publications

(13 citation statements)

References 40 publications

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“…The cellular mechanisms underlying this activity of sesamol are still not fully understood, but some observations, including ours, suggest the role of its potent anti-inflammatory and antioxidant activity which attenuates IR, body weight gain and hepatic steatosis [12][13][14]28]. Furthermore, we also demonstrated that sesamol amplified hepatic PPARα expression and reduced the activation of LXRα, SREBP-1c and FAS in HFD rats, which in turn markedly attenuated the interrelated steatosis and dyslipidemia through decreased fatty acid synthesis [7,8,11,24,26].…”

Section: Discussionsupporting

confidence: 58%

“…Furthermore, we observed a significant increase in serum leptin in HFD control rats [9], indicating leptin resistance which was also attenuated by sesamol. Interestingly, in our study, sesamol up-regulated PPARγ expression and it is well known that activation of PPARγ has potential to interfere with transcriptional pathways that are involved in oxidative stress and inflammatory responses [21][22][23][24]. We assume that this enhanced expression of PPARγ by sesamol negatively regulates the stimulus-dependent activation of P-JNK, IKK and NF-κB, and dysregulated production of numerous adipocytokines that promote IR [1,2,20,22,25].…”

Section: Discussionmentioning

confidence: 53%

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Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS

Sharma

Bharti

Bhatia

et al. 2012

The Journal of Nutritional Biochemistry

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 53%

Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS

Sharma

Bharti

Bhatia

et al. 2012

The Journal of Nutritional Biochemistry

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“…It also plays a vital role in cardioprotection through various mechanisms such as regulation of endothelial nitric oxide synthase (eNOS), angiotensin type 2 receptor expression [26,27]. Moreover, guggulipids also have both PPAR-and PPAR-agonistic activity [28], thus exerting a dual effect modulating glucose and lipid metabolism, which is further responsible for the cardioprotective activity. Thus, taking into consideration these molecular mechanisms of guggul extract, it could be used to prevent the diabetic cardiomyopathy as is observed in the present study.…”

Section: Resultsmentioning

confidence: 99%

Commiphora mukul Prevents Myocardial Dysfunction in Streptozotocin Induced Diabetic Rats

Barve¹,

Bhonsle²

2014

TOPHARMCJ

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Abstract:The objective of this study is to evaluate the effect of ethyl acetate extract of Commiphora mukul (guggul) (EACM) in streptozotocin (STZ) induced diabetic cardiomyopathy in rats. Diabetes was induced in rats with STZ (45 mg/kg, i.p). The animals were divided in four groups: I-normal control, II-diabetic control, III-diabetic animals treated with EACM (400 mg/kg/day, p.o) and IV-normal animals treated with EACM (400 mg/kg/day, p.o).Cardiomyopathy developed after eight weeks of induction of diabetes. The biochemical parameters (glucose, triglycerides, cholesterol, LDL, HDL, CKMB, LDH) were evaluated at regular intervals. The hemodynamic measurements (LVDEP, Mean BP, Max dP/dT, Min dP/dT, ST segment and QT interval) were done on the 8 th week. Standardized EACM contained 3.36% w/w of guggulsterones. There were significant changes observed in the biochemical, hemodynamic and histological parameters of diabetic animals indicating induction of diabetic cardiomyopathy, whereas diabetic animals treated with EACM for eight weeks showed significant improvement in these parameters which serve as diabetic and cardiac markers. The present study reveals that EACM is effective in preventing diabetes induced myocardial dysfunction. This might be due to its efficacy in (a) normalizing the metabolic disturbances by acting as Farnesoid X receptor antagonist (FXR) or PPAR-alpha and PPAR-gamma agonist thereby regulating the lipid and glucose metabolism, (b) having a cardioprotective effect through various mechanisms such as regulation of endothelial nitric oxide synthase (eNOS), angiotensin type 2 receptor expression etc or (c) both. Thus, guggul might be a promising candidate to be evaluated for clinical efficacy in diabetic patients for the prevention of cardiomyopathy.

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“…Previous results indicated that the expression of PPAR-γ mRNA is increased in adipose tissue of the obese subjects [29,30]. To determine whether PPAR-γ is involved in the mesenteric adipose tissue function, we examined PPAR-γ gene expression in the mesenteric adipose tissue.…”

Section: Adipose Tissue Lipolysis and Gene Expression At Different Admentioning

confidence: 99%

Human Mesenteric Adipose Tissue Plays Unique Role Versus Subcutaneous and Omental Fat in Obesity Related Diabetes

Yang

Chen²,

Clements³

et al. 2008

Cell Physiol Biochem

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Background/Aims: Obesity is a common and rapidly growing health problem today. Obesity is characterized by the increase of body fat and an excess of total body fat and, in particular, visceral fat accumulation, is considered to be a risk factor for type 2 diabetes mellitus. To determine whether the malfunction of the mesenteric adipose tissue plays an important role in the diabetic related metabolic syndrome, in this study, lipolysis and gene expression in the subcutaneous, omental and mesenteric adipose tissue of the diabetic subjects were evaluated. Methods: Lipolysis and real time PCR were utilized to determine adipocyte function. Results: Basal adipose tissue glycerol release is higher in diabetics than that of the non diabetics in all three fat depots. Isoproterenol (ISO) significantly increases glycerol release in subcutaneous, omental and mesenteric adipose tissues of non diabetic subjects but it stimulated glycerol release was significantly impaired in all three fat depots of the diabetic subjects. Gene expression studies indicate that leptin, Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), Fatty acid translocase (FAT/CD36) and 11β-hydroysteroid dehydrogenase (HSD) gene expression were significantly up regulated in the mesenteric adipose tissue of the diabetic patients. Conclusion: Human mesenteric adipose tissue in obese diabetic subjects has high basal glycerol release and impaired isoproterenol stimulated glycerol release. The obesity-related gene expressions in the mesenteric adipose tissue are up regulated, suggesting that the alterations of these genes in mesentery adipose depot may play a critical role in insulin resistance of type 2 diabetes and metabolic syndrome.

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Identification of a novel agonist of peroxisome proliferator-activated receptors α and γ that may contribute to the anti-diabetic activity of guggulipid in Lepob/Lepob mice

Cited by 22 publications

References 40 publications

Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS

Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS

Commiphora mukul Prevents Myocardial Dysfunction in Streptozotocin Induced Diabetic Rats

Human Mesenteric Adipose Tissue Plays Unique Role Versus Subcutaneous and Omental Fat in Obesity Related Diabetes

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