Effect of the orlistat on serum endotoxin lipopolysaccharide and adipocytokines in South Asian individuals with impaired glucose tolerance

Dixon, Anthony; Valsamakis, Georgios; Hanif, Moghees; Field, Annmarie; Boutsiadis, Anastasios; Harte, Alison; McTernan, P. G.; Barnett, Anthony; Kumar, Sudhesh

doi:10.1111/j.1742-1241.2008.01800.x

Cited by 29 publications

(44 citation statements)

References 22 publications

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“…The decrease of TNF-a levels observed was in line with that reported by Kiortsis et al [55], but in contrast to that shown by Harrison et al [56] whereby TNF-a levels were significantly higher in the orlistat group compared with controls in overweight subjects with nonalcoholic steatohepatitis. On the other hand, our results were in line with those reported by Dixon et al [40], who reported that 1 year of dietary treatment with orlistat results in a greater increase in ADN, compared with dietary treatment alone in South Asian individuals with IGT.…”

Section: Control Groupsupporting

confidence: 95%

“…As with our study, Dixon et al reported an improvement of lipid profile, and especially triglycerides, after 1 year of dietary treatment with orlistat compared with dietary treatment alone in South Asian individuals with impaired glucose tolerance (IGT) [40]. Also Filippatos et al showed the positive effects of orlistat on lipid profile, both in monotherapy or in combination with other drugs such as fenofibrate [41,42] or ezetimibe [43], with combination therapy having a more favorable effect on improving metabolic parameters in overweight and obese patients compared with each monotherapy.…”

Section: Discussionsupporting

confidence: 76%

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Comparison of orlistat treatment and placebo in obese type 2 diabetic patients

Derosa¹,

Maffioli²,

Salvadeo³

et al. 2010

Expert Opinion on Pharmacotherapy

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Section: Control Groupsupporting

confidence: 95%

Section: Discussionsupporting

confidence: 76%

Comparison of orlistat treatment and placebo in obese type 2 diabetic patients

Derosa¹,

Maffioli²,

Salvadeo³

et al. 2010

Expert Opinion on Pharmacotherapy

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“…Indeed, fat deposition compromises intestinal permeability, liver function and the ability of Kuppfer cells to adsorb endotoxin [25], [26], whose circulating concentration is, therefore, increased. This in turn, mediates chronic low-grade of inflammation through the activation of TLR and the inflammosome pathway to exacerbate the insulin resistant state [27]–[30]. In agreement with these observation LPS plasma concentration was increased in obese individuals carrying the “at-risk” GTA genotype, suggesting a correlation between obesity and microbial translocation that could be responsible for the maintenance of the inflammatory state at systemic level.…”

Section: Discussionsupporting

confidence: 66%

Vitamin D Receptor Gene Polymorphisms Are Associated with Obesity and Inflammosome Activity

et al. 2014

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To explore the mechanisms underlying the suggested role of the vitamin D/vitamin D receptor (VDR) complex in the pathogenesis of obesity we performed genetic and immunologic analyses in obese and non-obese Saudi individuals without other concomitant chronic diseases. Genomic DNA was genotyped for gene single nucleotide polymorphisms (SNPs) of VDR by allelic discrimination in 402 obese (body mass index –BMI≥30 kg/m2) and 489 non-obese (BMI<30 kg/m2) Saudis. Q-PCR analyses were performed using an ABI Prism 7000 Sequence Detection System. The inflammosome pathway was analysed by PCR, cytokines and plasma lipopolysaccaride (LPS) concentrations with ELISA assays. Results showed that the VDR SNPs rs731236 (G) (TaqI) and rs1544410 (T) (Bsm-I) minor allele polymorphisms are significantly more frequent in obese individuals (p = 0.009, β = 0.086 and p = 0.028, β = 0.072, respectively). VDR haplotypes identified are positively (GTA) (p = 0.008, β = 1.560); or negatively (ACC) (p = 0.044, β = 0.766) associated with obesity and higher BMI scores. The GTA "risk" haplotype was characterized by an up-regulation of inflammosome components, a higher production of proinflammatory cytokines (p<0.05) and a lower VDR expression. Plasma LPS concentration was also increased in GTA obese individuals (p<0.05), suggesting an alteration of gut permeability leading to microbial translocation. Data herein indicate that polymorphisms affecting the vitamin D/VDR axis play a role in obesity that is associated with an ongoing degree of inflammation, possibly resulting from alterations of gut permeability and microbial translocation. These results could help the definition of VDR fingerprints that predict an increased risk of developing obesity and might contribute to the identification of novel therapeutic strategies for this metabolic condition.

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“…Several teams have reported a relationship between impaired GI permeability and the translocation of live bacteria or LPS fragments into the bloodstream with the development of TD2 [178][179][180]. Translocation of bacterial fragments or whole bacteria into the systemic circulation leads to chronic immune activation and low-grade inflammation, which is the hallmark of metabolic endotoxemia as discussed previously.…”

Section: Increased Intestinal Permeability In Patients With Type 2 DImentioning

confidence: 93%

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

Morris¹,

et al. 2016

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There is a growing awareness that gut commensal metabolites play a major role in host physiology and indeed the pathophysiology of several illnesses. The composition of the microbiota largely determines the levels of tryptophan in the systemic circulation and hence, indirectly, the levels of serotonin in the brain. Some microbiota synthesize neurotransmitters directly, e.g., gamma-amino butyric acid, while modulating the synthesis of neurotransmitters, such as dopamine and norepinephrine, and brain-derived neurotropic factor (BDNF). The composition of the microbiota determines the levels and nature of tryptophan catabolites (TRYCATs) which in turn has profound effects on aryl hydrocarbon receptors, thereby influencing epithelial barrier integrity and the presence of an inflammatory or tolerogenic environment in the intestine and beyond. The composition of the microbiota also determines the levels and ratios of short chain fatty acids (SCFAs) such as butyrate and propionate. Butyrate is a key energy source for colonocytes. Dysbiosis leading to reduced levels of SCFAs, notably butyrate, therefore may have adverse effects on epithelial barrier integrity, energy homeostasis, and the T helper 17/regulatory/T cell balance. Moreover, dysbiosis leading to reduced butyrate levels may increase bacterial translocation into the systemic circulation. As examples, we describe the role of microbial metabolites in the pathophysiology of diabetes type 2 and autism.

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Effect of the orlistat on serum endotoxin lipopolysaccharide and adipocytokines in South Asian individuals with impaired glucose tolerance

Cited by 29 publications

References 22 publications

Comparison of orlistat treatment and placebo in obese type 2 diabetic patients

Comparison of orlistat treatment and placebo in obese type 2 diabetic patients

Vitamin D Receptor Gene Polymorphisms Are Associated with Obesity and Inflammosome Activity

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

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