rifampin and Metabolic-Syndrome

The pregnane X receptor (PXR) is a nuclear receptor that is traditionally thought to be specialized for sensing xenobiotic exposure. In concurrence with this feature PXR was originally identified to regulate drug-metabolizing enzymes and transporters. During the last ten years it has become clear that PXR harbors broader functions. Evidence obtained both in experimental animals and humans indicate that ligand-activated PXR regulates hepatic glucose and lipid metabolism and affects whole body metabolic homeostasis. Currently, the consequences of PXR activation on overall metabolic health are not yet fully understood and varying results on the effect of PXR activation or knockout on metabolic disorders and weight gain have been published in mouse models. Rifampicin and St. John's wort, the prototypical human PXR agonists, impair glucose tolerance in healthy volunteers. Chronic exposure to PXR agonists could potentially represent a risk factor for diabetes and metabolic syndrome. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

Topics: Animals; Diabetes Mellitus; Gene Expression Regulation; Gluconeogenesis; Glucose; Glycolysis; Humans; Hypericum; Inactivation, Metabolic; Lipogenesis; Liver; Metabolic Syndrome; Pregnane X Receptor; Receptors, Steroid; Rifampin; Signal Transduction

Over recent years, the link between obesity, metabolic syndrome and Hidradenitis suppurativa (HS) has been explored. It has been demonstrated that HS patients have a high prevalence of the metabolic syndrome and an increased frequency of insulin resistance. The objective of our study is to estimate the effectiveness of an oral supplementation based on myo-inositol (MI), folic acid and liposomal magnesium (Levigon. Twenty subjects with HS and an impaired glucose metabolism were enrolled. Group A: 10 subjects received for 6 months MI 2000 mg, liposomal magnesium and folic acid associated to topical antibiotic therapy (clindamycin gel 1%), systemic antibiotic therapy (clindamycin 300 mg b.i.d. and rifampicin 600 mg daily for 6 weeks) and a normocaloric diet group B: 10 subjects received topical and systemic antibiotic therapy associated to a normocaloric diet for 6 months.. After 6 months group A patients showed an average reduction of Sartorius Score from 38.3±7.75 to 27.3±13.53 (P value <0.04) while in the control group there was a reduction of the Sartorius from 38.4±7.88 to 31.1±8.02 (P value =0.55). Moreover in group A Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly reduced from 2.43±0.35 to 2.1±0.31 (P<0.01) whereas in group B HOMA-IR did not significantly decrease (2.51±0.65 at T0 at 2.40±0.67 at T1).. Our study underlines the importance of the evaluation of metabolic profile in patients with HS. Moreover, it suggests that the supplementation of MI, folic acid and liposomal magnesium in HS can improve the efficacy of concomitant therapies and the metabolic profile.

Topics: Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Clindamycin; Dietary Supplements; Drug Combinations; Drug Therapy, Combination; Energy Intake; Folic Acid; Glucose Intolerance; Hidradenitis Suppurativa; Humans; Inositol; Insulin Resistance; Liposomes; Magnesium; Metabolic Syndrome; Prevalence; Rifampin; Severity of Illness Index