calcipotriene and Obesity

Several factors have been shown to affect psoriasis pathogenesis, clinical presentation and treatment response.. The aim of this study was to investigate the potential relationship between patients' baseline characteristics and the efficacy of calcipotriol-betamethasone ointment in patients with mild to moderate plaque psoriasis and to evaluate whether the efficacy is consistent across subgroups.. Using data from the therapeutic equivalence study on patients with plaque psoriasis, post hoc analyses were performed to evaluate the impact of baseline demographic and disease characteristics, habits and comorbidities on the response to treatment with calcipotriol-betamethasone ointment.. Body mass index (BMI) and obesity were each independently associated (univariate analysis, p < 0.05) with reduction in modified Psoriasis Area and Severity Index (mPASI) and PASI75 (≥75% improvement in mPASI from baseline). Increased body weight is more common in patients with late-onset psoriasis. There was a significant trend for lower response rates with increasing BMI (p = 0.007) and obesity (p = 0.003). The odds of achieving PASI75 is 2.3 times lower for obese compared to normal-weight subjects.If patients with obesity or hypertension were treated with calcipotriol-betamethasone, they were still more likely to achieve PASI75 after 4-week treatment compared to vehicle (p < 0.001).. Increased BMI and obesity present risk factors for reduced treatment effectiveness. Importantly, the efficacy of calcipotriol-betamethasone ointment was consistent in all subgroups.

Topics: Adult; Anti-Inflammatory Agents; Betamethasone; Body Mass Index; Body Weight; Calcitriol; Dermatologic Agents; Double-Blind Method; Drug Combinations; Female; Humans; Male; Obesity; Ointments; Psoriasis; Severity of Illness Index

The orphan nuclear receptor Nur77 is an important factor regulating metabolism. Nur77 knockout mice become obese with age, but the cause of obesity in these mice has not been fully ascertained. We attempted to explain the cause of obesity in Nur77 knockout mice from the perspective of the gut microbiota and to investigate the inhibitory effect of calcipotriol combined with BRD9 inhibitor (iBRD9) on obesity.. Eight-week-old wild-type mice and Nur77 knockout C57BL/6J mice were treated with calcipotriol combined with iBRD9 for 12 weeks. Mouse feces were collected and the gut microbiota was assessed by analyzing 16S rRNA gene sequences. The bacterial abundance difference was analyzed, and the intestinal mucosal tight junction protein, antimicrobial peptide, and inflammatory cytokine mRNA levels of the colon and serum LPS and inflammatory cytokine levels were measured.. Calcipotriol combined with iBRD9 treatment reduced the body weight and body fat percentage in Nur77 knockout mice. In the gut microbiota of Nur77 knockout mice, the relative abundances of Lachnospiraceae and Prevotellaceae decreased, and Rikenellaceae increased; while Rikenellaceae decreased after treatment (p < 0.05). Correspondingly, the mRNA levels of intestinal mucosal tight junction proteins (occludin (Ocln), claudin3 (Cldn3)) in the colons of Nur77 knockout mice were significantly decreased, and they increased significantly after treatment (p < 0.001). The mRNA levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)) were significantly increased in Nur77 knockout mice, and TNF-α and IL-6 levels were significantly decreased after treatment (p < 0.05, <0.01, or <0.001). The levels of serum LPS, TNF-α, and IL-1β in Nur77 knockout mice were significantly increased (p < 0.05). Serum LPS, TNF-α, and IL-6 levels were significantly decreased after treatment (p < 0.05 or <0.01).. Calcipotriol combined with iBRD9 can regulate the gut microbiota, improve intestinal mucosal barrier function, reduce LPS absorption into the blood, and alleviate obesity in Nur77 knockout mice.

Topics: Animals; Calcitriol; Cytokines; Gastrointestinal Microbiome; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Receptor Subfamily 4, Group A, Member 1; Obesity; Transcription Factors

To evaluate the literature to determine which oral and topical medications are most effective in the treatment of insulin resistance obesity-related acanthosis nigricans (IRORAN).. A MEDLINE literature search was conducted (1950-January 2008) using the search terms acanthosis nigricans (AN), metformin, rosiglitazone, octreotide, retinoic acid, acitretin, etretinate, and isotretinoin. The search was limited to articles on treatment of IRORAN in humans written in the English language. Articles were retrieved and all references were reviewed.. Articles selected for inclusion were limited to AN related to obesity with no other underlying etiology. Clinical trials and case reports using monotherapy were included.. Metformin, rosiglitazone, octreotide, vitamin D analogs, and retinoic acid have been used in the treatment of IRORAN. In one randomized trial, metformin 500 mg 3 times daily was compared with rosiglitazone 4 mg once daily. Neither treatment demonstrated significant improvements in AN; however, rosiglitazone did significantly decrease serum insulin levels. In a second clinical trial and in several case reports, AN and hyperinsulinemia did show improvement with metformin treatment. After a 6-month period, octreotide improved IRORAN, body weight, and glucose/insulin response to a meal. The improvements persisted for 6 additional months after discontinuation of octreotide. Vitamin D analogs and retinoids produced inconsistent results in 5 separate case reports.. IRORAN is a growing problem, particularly in children and adolescents, secondary to the increase in the prevalence of obesity. Treatment of IRONAN should focus on reversal of the underlying hyperinsulinemia. Patients with IRORAN may benefit from a trial of metformin for improvement of lesions and underlying hyperinsulinemia.

Topics: Acanthosis Nigricans; Adolescent; Adult; Calcitriol; Humans; Hyperinsulinism; Hypoglycemic Agents; Insulin Resistance; Metformin; Obesity; Octreotide; Retinoids; Rosiglitazone; Thiazolidinediones; Vitamin D