Induced Weight Gain Research Articles

Post-transplant Diabetes Mellitus: What Physicians Need to Know.

Post-transplant diabetes mellitus (PTDM) is a common problem among solid organ transplant recipients contributing to morbidity and affecting patient as well as graft survival adversely. It can occur at any period following transplantation, but maximum incidence is observed in the first few months, with a second peak after a few years after transplantation. The pathogenesis is complex and poorly understood, however, it is associated with both dysfunctional beta-cells and insulin resistance. Both nonpharmacologic and antidiabetic therapies are important for adequate glycemic control. This point of view article provides a short review on PTDM in solid organ transplantation (SOT) recipients from a general physician's perspective.

Chronic Spontaneous Urticaria in Adult Patients: Evaluating the Effect of Loratadine on Weight and Metabolic Syndrome

Antihistamine is standard chronic spontaneous urticaria (CSU) therapy. Weight gain is a side effect of concern as prolonged high dose therapy is common. We investigated the effects of 12-weeks loratadine therapy on weight, appetite and parameters of metabolic syndrome (MetS). A cohort study was performed involving CSU patients aged ≥18 years. Patients with diseases or on drugs affecting weight or appetite were excluded. CSU was treated according to standard management. Weight, height, waist circumference (WC), body mass index (BMI) and blood pressure (BP), Urticaria Activity Score 7 (UAS7), Dermatology Life Quality Index (DLQI), hunger and satiety questionnaire, fasting blood sugar (FBS) and fasting lipid profile (FLP) were obtained at baseline, week 6 and week 12. Loratadine cumulative dose were determined. Thirteen (33.33 %) males and 26 (66.67 %) females aged 33.00 (12.00) years participated. Median weight was 62.55 (18.30) kg, BMI 24.60 (6.80) kg/m2, 13(33.33%) patients had normal weight, 12 (30.77%) overweight, 11 (28.21%) obese and 3 (7.69%) underweight. Significant weight gain was observed at week 6, 67.56 ± 16.14 kg vs 68.16 ± 16.95 kg, p < 0.05 and 67.56 ± 16.14 kg vs 64.73 ± 14.60 kg, p = 0.04 at week 12. Changes in BMI, WC, BP, FBS and FLP were insignificant. Three patients developed MetS. Hunger and satiety scores were unaffected. Loratadine induced weight gain despite no effects on appetite. Weight should be monitored in patients on long term loratadine therapy. Keywords: Urticaria; loratadine; weight gain; metabolic syndrome; appetite

Obesity and bariatric surgery in adults living with severe mental illness: perceptions and clinical challenges.

Overweight and obesity are twice as likely to develop in people living with severe mental illness (SMI), compared with those without. Many factors contribute to this, such as reduced physical activity and the use of certain medications that induce weight gain. Obesity contributes to the premature mortality seen in people living with SMI, as it is one of the fundamental risk factors for cardiovascular disease and diabetes. Bariatric surgery is an effective treatment option, although patients living with SMI might face stigma when being considered for surgical intervention. This article proposes a discussion around obesity and bariatric surgery in patients living with SMI. It will also reflect on the challenges faced by healthcare professionals and patients living with SMI and obesity, when considering appropriate treatments for weight loss. The paper utilises a fictional case, informed by contributions from a lived experience author, to explore bariatric surgery in people living with SMI.

Long-term treatment of antipsychotics and combined therapy with other psychotropic medications inducing weight gain in patients with non-affective psychotic disorder: Evidence from GROUP, a longitudinal study

Introduction: Antipsychotics (APs) can cause weight gain. Little is known about changes in weight when APs are combined with other psychotropics. This study examines the weight change in patients undergoing long-term treatment with APs or with AP combined with other psychotropics.Methods: Patients with non-affective psychotic disorder from the GROUP study were divided into three groups: AP medication group (APm) (n = 100), AP in combination with other psychotropics (APc) (n = 73), and medication-free (Meds-free) (n = 100). Weight change was examined at inclusion and after three years using a paired-sample t-test. An Independent-sample t-test was performed to evaluate weight change among patients taking clozapine, olanzapine, and quetiapine and individuals not taking these medications. Linear regression was performed to evaluate the association between covariates and weight.Results: Patients in the APm group [mean = 1.800 kg, t(99)=2.849, 95% CI(0.546, 3.054), p = 0.005] and the APc group [mean = 1.877 kg, t(72)=2.688, 95% CI(0.485, 3.268), p = 0.009] showed significant weight gain. Patients taking clozapine, olanzapine or quetiapine showed significant weight gain compared to those not taking these medications [mean difference=1.707 kg, t(271)= 2.061, 95% CI(0.077, 3.337), p = 0.040)].Conclusion: Patients receiving APs and APs with other psychotropics gain weight during long-term treatment. It is possible that weight gain is mainly driven by APs.

Effects of psychotropic switches on weight change: a prospective cohort study

IntroductionMany psychotropic drugs can induce weight gain with differences in their metabolic risk profiles (i.e. high, medium or low-risk).ObjectivesTo compare the weight evolution of patients switching versus patients keeping their psychotropic drugs with different risk-profiles.MethodsData for patients switching or keeping the same drug were obtained from the Psyclin (from 2007 to 2015) and Psymetab (2007- 2019) cohort studies, conducted at the Lausanne University Hospital, Switzerland. Patients either switched from a high to a low-risk, a high to a medium-risk, a medium to a low-risk drug, or for a drug with the same risk category. Patients not switching either kept a high, medium or low-risk drug. The evolution of weight is currently being analyzed using a linear mixed-effect model.ResultsPreliminary results showed that switching from a high to low-risk molecule had the strongest impact on weight changes. The analysis being ongoing, the quantitative results will be presented at the congress.ConclusionsSwitching from a high-risk to a low-risk molecule is likely to have the strongest impact on weight changes.DisclosureNo significant relationships.

Clinical, genetic and environmental influences on weight gain and metabolic disorders induced by psychotropic drugs

Introduction Weight gain and obesity are important health problems associated with psychiatric disorders and/or with psychotropic drug treatments. There is a high inter-individual variability in the susceptibility to drug induced weight gain and/or other cardiometabolic disorders.ObjectivesTo study the genetic and environmental risk factors for weight gain and onset of metabolic syndrome during psychotropic treatmentMethodsAnalysis in PsyMetab, a large (n>3000) ongoing longitudinal prospective cohort study investigating cardiometabolic disorders in psychiatric patients.ResultsAside from well-known clinical risk factors for metabolic worsening (e.g. young age, first episode status, rapid weight gain during the first month of treatment and/or low initial BMI), additional risk factors have been recently identified. We showed an inverse association between socio-economic status (SES) and worsening of cardiometabolic parameters, adult patients with a low SES having a three-fold higher risk of developing metabolic syndrome over one year versus patients with a high SES (n=366). In addition, a causal inverse effect of educational attainment on BMI was revealed using Mendelian randomization in the UKBiobank (n=30’069). Results from an epigenome-wide association study (EWAS) performed in 78 patients before and after one month of treatment and from a genome-wide association study (GWAS) in 1924 patients will also be presented.ConclusionsDifferences in clinical, genetic and environmental factors contribute to the differences in weight gain and metabolic disorders induced by psychotropic drugs. When starting a psychotropic drug at risk, a prospective monitoring of clinical (e.g. weight and blood pressure) and biochemical (fasting glucose, lipid levels) parameters is essential.DisclosureProf. Eap received honoraria for conferences or teaching CME courses from Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Vifor-Pharma, and Zeller in the past 3 years. The other authors report no potential conflicts of interest. This work has

The Impact of Probiotic Supplementation on Cognitive, Pathological and Metabolic Markers in a Transgenic Mouse Model of Alzheimer's Disease.

Brain degenerative disorders such as Alzheimer’s disease (AD) can be exacerbated by aberrant metabolism. Supplementation with probiotic bacteria is emerging as a promising preventative strategy for both neurodegeneration and metabolic syndrome. In this study, we assess the impact of the Lab4b probiotic consortium on (i) cognitive and pathological markers of AD progression and (ii) metabolic status in 3xTg-AD mice subjected to metabolic challenge with a high fat diet. The group receiving the probiotic performed better in the novel object recognition test and displayed higher hippocampal neuronal spine density than the control group at the end of the 12 weeks intervention period. These changes were accompanied by differences in localised (brain) and systemic anti-inflammatory responses that favoured the Probiotic group together with the prevention of diet induced weight gain and hypercholesterolaemia and the modulation of liver function. Compositional differences between the faecal microbiotas of the study groups included a lower Firmicutes:Bacteroidetes ratio and less numbers of viable yeast in the Probiotic group compared to the Control. The results illustrate the potential of the Lab4b probiotic as a neuroprotective agent and encourage further studies with human participants.

Reproducibility of a High Fat Diet Induced Weight Gain Over Independent Years

Susceptibility to dietary‐induced excessive weight gain is a product of the interaction between genetics and the environment (e.g., high fat diet, HFD). Unfortunately, research on the effects of a HFD has been confounded by uncontrolled obesogenic environments. Thus, this study investigated the reproducibility of weight gain and energy intake over 3 independent consecutive years with exposure to a tightly regulated obesogenic environment: male, outbred Sprague‐Dawley rats, 140‐160g, identical macronutrient and fatty acid composition with a caloric density of 5.24 kcal/g for 8‐wk periods. A CHOW diet which is lower in fat (3.1 kcal/g) served as a standard control. Daily data was accrued to determine means and standard deviations (SDs) of peak cumulative (additive weekly) and average periodic (isolated weekly) values, showing weight gain in rats fed a HFD in years 2018 (n=11), 2019 (n=12), and 2020 (n=14) resembled (insignificant) each other. This response was not observed with energy intake data. When heterogeneously distributed weight gain values in the HFD population were separated into tertiles, the lower and upper tertiles were designated as obesity resistant (OR) and obesity prone (OP), respectively. Both OP and OR means and SDs of weight gain resembled each other between the 3 years when studied under similar cumulative and periodic conditions whereas energy intake values did not. Percentage differences in weight gain between the 3 years under cumulative and periodic conditions were: (1) 3‐8% for HFD rats for both conditions, (2) 3‐7% and 1‐5% for OP rats, 0‐10% and 0‐12% for OR rats, respectively. Between the 3 years, the mean and SDs of feeding efficiency (FE; weight gain/ energy intake), of HFD rats were insignificant; the least variability between the years (1‐3%) was observed in OP rats. Within each year, weight gain values between HFD and CHOW rats under both conditions were insignificant except for year 2020 under cumulative conditions; weight gain for OP rats was significantly greater than OR rats (~ 25‐35%) under cumulative conditions. Under periodic condition, all rat populations exhibited significant maximal weight gain values at week 1, promptly decaying by 40‐50% at week 4 with significance between week 1‐2 and 2‐3; all values decayed to insignificance between contiguous weeks 3‐8. This periodic profile implied that the significant ascending (augmenting) weekly values associated with cumulative profiling could be misrepresenting the nature of weight gain when cross‐sectional analysis of body weight is evaluated. Pearson correlation analysis of weight gain vs. energy intake among HFD rats showed that, despite a significant slope, 53% of the variability in weight gain could be explained by the variation in energy intake values.ConclusionConsidering a history of polygenic patterns of inheritance in HFD‐fed rats, and the use of multiple litters in this study, weight gain and FE of HFD, OP and OR rats was perpetuated (reproduced) over 3 independent years, suggesting certain combination of alleles were obesogenic, the latter perhaps contributing to set‐point control.

METABOLIC SYNDROME IN PATIENTS WITH PSYCHOSIS USING SECOND-GENERATION ANTIPSYCHOTICS

Background: Persons with Schizophrenia are more likely to die from cardiovascular illness and are at a greater risk of developing obesity, diabetes mellitus (DM), hypertension (HTN), and dyslipidemias. Though the SGA were quite effective, their safety advantages have been questioned because of their propensity to induce weight gain and alter glucose,lipid metabolism. Objectives: 1.To study the incidence of metabolic syndrome (MS) due to selected SGA 2.To compare any differences in the metabolic profile of patients on various antipsychotics. Methodology: A Study was done for about a year among 120 Drug Naive patients with the diagnosis of schizophrenia or acute psychosis as per ICD 10 criteria,attending psychiatry OPD and were selected by systematic sampling method into four groups.With the Group (A) receiving Olanzapine, group (B) Risperidone, group (C) Quetiapine, group (D) Aripiprazole.Each group consisting of 30 patients.After 12 weeks of medication,Patients were screened for the MS using NCEP- ATP III criteria.Data was collected and analyzed using SPSS software,ANOVA was used to assess the significance of the difference of mean values of different parameters in between groups. Results: In the study concerning age group, majority of patients belong to 20-30(41.67%) yrs.There were no significant gender differences with 54.17% males and 45.80% females. Among 120 patients, 13(10.83%) patients developed MS after three months of continuous antipsychotic drug therapy. Among those who received Olanzapine and Risperidone, five patients from each group developed MS, and three patients who received Quetiapine fulfilled the criteria of MS.No patient on Aripiprazole developed MS. Conclusion: The psychiatrist needs to be aware of the potential metabolic side effects of antipsychotic medication and to include them in the risk/benefit assessment when choosing a specific antipsychotic. Multidisciplinary assessment of psychiatric and medical conditions is needed.

Olanzapine-samidorphan combination tablets for the treatment of schizophrenia and bipolar I disorder - what is it, and will it be used?

ABSTRACT Introduction Although olanzapine remains one of the most efficacious antipsychotic medications for the treatment of schizophrenia, there are significant tolerability concerns related to its weight and metabolic profile. Olanzapine-samidorphan combination tablets (OLZ/SAM), branded as Lybalvi, is a newly FDA approved formulation aimed at attenuating antipsychotic induced weight gain via modulation of the endogenous opioid system with samidorphan, while retaining the robust antipsychotic efficacy of olanzapine. Areas covered We reviewed the published literature of OLZ/SAM for the management of schizophrenia using the US National Library of Medicine’s PubMed.gov resource. Topics covered in this narrative review include the pharmacokinetics, pharmacodynamics, efficacy, and tolerability of OLZ/SAM. Expert Opinion OLZ/SAM is an effective and well-tolerated pharmacologic option in mitigating olanzapine induced weight gain while retaining olanzapine’s efficacy. OLZ/SAM cumulatively tends to attenuate weight gain rather than promote weight loss. Effect on metabolic laboratory variables appears limited. Additional research will be needed to determine its effectiveness compared to alternative strategies to attenuate antipsychotic induced weight gain.

410 Mild Maternal Undernutrition Results in a Premature Neonatal Leptin Surge and Resistance in Male Offspring to a High Fat Diet

OBJECTIVES/GOALS: Maternal undernutrition, a form of malnutrition, can alter neonatal leptin signaling and result in metabolic dysfunction in adulthood. We developed a mild undernutrition model to relate more to societys nutritional challenges and to test the hypothesis that a shift in the neonatal leptin surge would result in sex-specific metabolic changes. METHODS/STUDY POPULATION: We studied pups from undernourished dams which were calorically restricted by 20% (CR20) from embryonic day 15 until postnatal day (PND) 21. We tested 216 offspring from 11 Fed dams and 13 undernourished dams (CR20), detecting a leptin surge in control fed progeny at PND11. At 3 months of age, offspring from 3 dams per maternal nutrient status were either exposed to a 45% high fat diet (HFD) or control diet (10% fat) for 16 weeks. Anterior pituitary hormones were analyzed in the pituitary and serum of neonates and adults. To determine the mechanism of the phenotype observed in male adult offspring on the HFD, single cell RNA sequencing was used to analyze the pituitary, fat and liver. RESULTS/ANTICIPATED RESULTS: Offspring of CR20 dams had an early leptin surge peaking at PND8 and GH levels at PND1 were higher in CR20 progeny. Weights of both male and female CR20 offspring were lower and body lengths were shorter than controls. As adults, Fed mice from both sexes had increased weight gain with HFD. However, although CR20 females gained weight on the HFD, male progeny from CR20 dams did not gain weight on the HFD and appeared protected from impact. We found sex-specific changes in pituitary Gh, Ghrhr, and Ghsr mRNA levels. Single cell RNA sequencing of pituitary, fat and liver of male offspring showed significant regulation of transcripts in fat of male offspring from Fed dams that was not found in CR20 males when compared to control fed mice. DISCUSSION/SIGNIFICANCE: Mild undernutrition causes a prematurely high leptin surge and sex-specific growth responses to a HFD, including resistance to a HFD in underfed males. Transcript analysis in fat of males resistant to HFD induced obesity may reveal mechanisms that provide protection against HFD induced weight gain.

Extracts of Citrus Juice Processing Wastes Induce Weight Gain and Decrease Serum Glucose in Sprague-Dawley Rats

In this study, the safety and functionality of using citrus juice processing waste (CJPW) was confirmed. Large quantities of CJPW are generated on Jeju Island and cause environmental problems. CJPW extract (2,000 mg/kg) was administered intragastrically to male and female Sprague-Dawley (SD) rats for 14 days and the rats were analyzed. No general signs of toxicity were observed in SD rats administered CJPW extract. Feed intake did not differ between experimental and control animals. However, male and female rats administered CJPW extract had greater weight gain (102.9±5.53% and 114.15±6.89%, respectively) compared with the control animals. Higher weight gain was found in male and female experimental animals, but the difference was only significant in female animals. Serum analyses indicated that total protein and albumin, indicators of nutritional status, were significantly increased in animals administered CJPW. Further, serum glucose values were lower in male and female rats treated with CJPW (91.6±9.02% and 69.9±4.11%, respectively) compared with the controls; again, the difference was significant only for female animals. From the results of this study, CJPW can be considered as a safe material that does not induce toxicity in experimental animals. Therefore, CJPW is a potential raw material that can be used as a supplement in animal feed to help improve weight gain and achieve serum glucose con-trol.

Novel role of peroxisome proliferator activated receptor-α in valproic acid rat model of autism: Mechanistic study of risperidone and metformin monotherapy versus combination

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of heterogenous etiology exhibiting a challenge in understanding its exact neuro-pathophysiology. Recently, peroxisome proliferator activated receptor (PPAR)-α activation was found to play a fundamental role in neuroprotection and improving autistic-like-behaviors in experimental animal models of ASD through alleviating neuroinflammation, oxidative-stress, astrocyte reactivity, tauopathy in addition to its favorable role in metabolic regulation, thus attracting attention as a possible target in treatment of ASD.This study aimed to investigate the role of PPAR-α, astrocytic dysfunction and tauopathy in ASD and detect the possible neuroprotective effects of metformin (MET), through PPAR-α activation, and risperidone (RIS) either monotherapy or in combination in alleviating autistic-like-changes at behavioral and neurobiological levels in male Wistar rats.Pregnant female Wistar rats received valproic-acid (VPA) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic intra-peritoneal MET (100 mg/kg/day) and RIS (1 mg/kg/day) either monotherapy or in combination started from postnatal day (PND) 24 till PND61 (38 days).Prenatal VPA exposure simulated the autistic core behaviors associated with neurochemical and histopathological neurodevelopmental degenerative changes. Both MET and RIS either monotherapy or in combination were able to reverse these changes. The effect of MET was comparable to RIS. Moreover, MET was able to alleviate the RIS induced weight gain and improve cognitive functions highlighting its promising adjunctive role in alleviating ASD pathophysiology.Our study highlighted the favorable effects of MET and RIS both in monotherapy and in combination in alleviating the autistic-like-changes and proposed PPAR-α activation along with restoring astrocytes homeostasis as promising targets in novel therapeutic strategies in ASD.

Nocturnal Light Pollution Induces Weight Gain in Mice and Reshapes the Structure, Functions, and Interactions of Their Colonic Microbiota.

In mammals, the daily variation in the ecology of the intestinal microbiota is tightly coupled to the circadian rhythm of the host. On the other hand, a close correlation between increased body weight and light pollution at night has been reported in humans and animal models. However, the mechanisms underlying such weight gain in response to light contamination at night remain elusive. In the present study, we tested the hypothesis that dim light pollution at night alters the colonic microbiota of mice, which could correlate with weight gain in the animals. By developing an experimental protocol using a mouse model that mimics light contamination at night in urban residences (dLAN, dim light at night), we found that mice exposed to dLAN showed a significant weight gain compared with mice exposed to control standard light/dark (LD) photoperiod. To identify possible changes in the microbiota, we sampled two stages from the resting period of the circadian cycle of mice (ZT0 and ZT10) and evaluated them by high-throughput sequencing technology. Our results indicated that microbial diversity significantly differed between ZT0 and ZT10 in both LD and dLAN samples and that dLAN treatment impacted the taxonomic composition, functions, and interactions of mouse colonic microbiota. Together, these results show that bacterial taxa and microbial metabolic pathways might be involved with the mechanisms underlying weight gain in mice subjected to light contamination at night.

Olfactomedin 2 deficiency protects against diet-induced obesity

Background and aimsOlfactomedin 2 (OLFM2; also known as noelin 2) is a pleiotropic protein that plays a major role in olfaction and Olfm2 null mice exhibit reduced olfactory sensitivity, as well as abnormal motor coordination and anxiety-related behavior. Here, we investigated the possible metabolic role of OLFM2. MethodsOlfm2 null mice were metabolically phenotyped. Virogenetic modulation of central OLFM2 was also performed. ResultsOur data showed that, the global lack of OLFM2 in mice promoted anorexia and increased energy expenditure due to elevated brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT). This phenotype led to resistance to high fat diet (HFD)-induced obesity. Notably, virogenetic overexpression of Olfm2 in the lateral hypothalamic area (LHA) induced weight gain associated with decreased BAT thermogenesis. ConclusionOverall, this evidence first identifies central OLFM2 as a new molecular actor in the regulation of whole-body energy homeostasis.

Effect of pentoxifylline on colon cancer patients treated with chemotherapy (Part I).

Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties. To evaluate PTX effects on colon cancer patients treated with chemotherapy. Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX). Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group. PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence -all important parameters of cachexia.

The second-generation antipsychotic drug aripiprazole modulates the serotonergic system in pancreatic islets and induces beta cell dysfunction in female mice

Aims/hypothesisSecond-generation antipsychotic (SGA) drugs have been associated with the development of type 2 diabetes and the metabolic syndrome in patients with schizophrenia. In this study, we aimed to investigate the effects of two different SGA drugs, olanzapine and aripiprazole, on metabolic state and islet function and plasticity.MethodsWe analysed the functional adaptation of beta cells in 12-week-old B6;129 female mice fed an olanzapine- or aripiprazole-supplemented diet (5.5–6.0 mg kg−1 day−1) for 6 months. Glucose and insulin tolerance tests, in vivo glucose-stimulated insulin secretion and indirect calorimetry were performed at the end of the study. The effects of SGAs on beta cell plasticity and islet serotonin levels were assessed by transcriptomic analysis and immunofluorescence. Insulin secretion was assessed by static incubations and Ca2+ fluxes by imaging techniques.ResultsTreatment of female mice with olanzapine or aripiprazole for 6 months induced weight gain (p<0.01 and p<0.05, respectively), glucose intolerance (p<0.01) and impaired insulin secretion (p<0.05) vs mice fed a control chow diet. Aripiprazole, but not olanzapine, induced serotonin production in beta cells vs controls, likely by increasing tryptophan hydroxylase 1 (TPH1) expression, and inhibited Ca2+ flux. Of note, aripiprazole increased beta cell size (p<0.05) and mass (p<0.01) vs mice fed a control chow diet, along with activation of mechanistic target of rapamycin complex 1 (mTORC1)/S6 signalling, without preventing beta cell dysfunction.Conclusions/interpretationBoth SGAs induced weight gain and beta cell dysfunction, leading to glucose intolerance; however, aripiprazole had a more potent effect in terms of metabolic alterations, which was likely a result of its ability to modulate the serotonergic system. The deleterious metabolic effects of SGAs on islet function should be considered while treating patients as these drugs may increase the risk for development of the metabolic syndrome and diabetes.Graphical abstract

Effect of Beilschmedia obscura on the prevention of high fat/high sucrose diet induced metabolic syndrome on male Albino Wistar rats

IntroductionBeilschmiedia (Lauraceae) is a pantropical genus of about 287 species, distributed in tropical Asia and Africa used in traditional medicines to cure many diseases. This study aimed to explore biological properties of Beilschmiedia obscura (B. obscura) on the prevention and management of metabolic syndrome (MetS) features induced by High Fat/High Sucrose (HF/HS) diet in rats as therapeutic option. MethodsMetS was induced after administration of HF/HS diet followed by administration of B. Obscura powder at 5% or 10% for 21 days, while the control group received a chow diet and distilled water and the positive control group received the HF/HS diet and distilled water. At the end of the experiment, rats were sacrificed; the parameters of lipid profile, markers of oxidative stress, antioxidant status were evaluated. ResultsHF/HS diet successfully induced weight gain, oxidative stress and lipid profile disorders from rats. Treatment with powder of B. obscura at 10% than the 5% showed a reduction of body weight in treated groups and, anti-hyperlipidemic effect by improving lipid profile parameters. Triglycerides, Total cholesterol and LDL cholesterol levels were lower (p<0.05) and HDL-cholesterol levels higher in the treated groups compared to positive control. Inhibition of lipid peroxidation, and improvement protein thiols levels and catalase activity were also observed in treated groups. ConclusionThis study revealed that B. obscura whole plant was efficient in reducing biomarkers involved in metabolic syndrome and could efficiently help in its management by preventive effect.

High-fat western diet-consumption alters crystalline silica-induced serum adipokines, inflammatory cytokines and arterial blood flow in the F344 rat

Adipose tissue (AT) plays a central role in the maintenance of whole-body energy homeostasis through release of adipokines. High-fat Western diet (HFWD)-consumption contributes to obesity, disruption of adipocyte metabolism, chronic systemic inflammation, and metabolic dysfunction (MetDys). MetDys is associated with impaired lung function, pulmonary hypertension, and asthma. Thirty-five percent of adults in the U.S. have MetDys, yet the impact of MetDys on susceptibility to occupational hazards is unknown. The aim of this study was to determine the potential of HFWD-consumption to alter inhaled crystalline silica dust-induced metabolic responses. Six-wk old male F344 rats were fed a HFWD (45 kcal % fat, sucrose 22.2 % by weight) or standard rat chow (STD, controls), and exposed to silica-inhalation (6 h/d, 5 d/wk, 39 d; Min-U-Sil 5®, 15 mg/m3) or filtered air. Indices of MetDys and systemic inflammation were measured at 0, 4, and 8 wk following cessation of silica exposure. At 8 wk post-exposure, silica reduced serum leptin and adiponectin levels, and increased arterial pulse frequency. HFWD-consumption induced weight gain, altered adipokines, liver, kidney, and pancreatic function, and increased tail artery blood flow. At 8 wk in HFWD + SIL-treated animals, the levels of serum pro-inflammatory cytokines (IFN-γ, CXCL-1, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-10 and IL-13) were increased compared to STD + SIL but were less than HFWD + AIR-induced levels. In conclusion, consumption of a HFWD altered silica-induced metabolic responses and silica exposure disrupted AT endocrine function. These findings demonstrate previously unknown interactions between HFWD-consumption and occupational silica exposure.

Assessment of the Effects of Dietary Vitamin D Levels on Olanzapine-Induced Metabolic Side Effects: Focus on the Endocannabinoidome-Gut Microbiome Axis.

Vitamin D deficiency is associated with poor mental health and dysmetabolism. Several metabolic abnormalities are associated with psychotic diseases, which can be compounded by atypical antipsychotics that induce weight gain and insulin resistance. These side-effects may be affected by vitamin D levels. The gut microbiota and endocannabinoidome (eCBome) are significant regulators of both metabolism and mental health, but their role in the development of atypical antipsychotic drug metabolic side-effects and their interaction with vitamin D status is unknown. We studied the effects of different combinations of vitamin D levels and atypical antipsychotic drug (olanzapine) exposure on whole-body metabolism and the eCBome-gut microbiota axis in female C57BL/6J mice under a high fat/high sucrose (HFHS) diet in an attempt to identify a link between the latter and the different metabolic outputs induced by the treatments. Olanzapine exerted a protective effect against diet-induced obesity and insulin resistance, largely independent of dietary vitamin D status. These changes were concomitant with olanzapine-mediated decreases in Trpv1 expression and increases in the levels of its agonists, including various N-acylethanolamines and 2-monoacylglycerols, which are consistent with the observed improvement in adiposity and metabolic status. Furthermore, while global gut bacteria community architecture was not altered by olanzapine, we identified changes in the relative abundances of various commensal bacterial families. Taken together, changes of eCBome and gut microbiota families under our experimental conditions might contribute to olanzapine and vitamin D-mediated inhibition of weight gain in mice on a HFHS diet.