The Effects of Gluten on Weight Gain, Hematological, Biochemical, and Various Endocrinological Parameters.

BACKGROUND/AIMS:  This study is aimed to compare the effects of nutrition which has been enriched with different amounts of gluten to gluten-free diets on weight gain, diabetogenic state, hematological, and biochemical parameters. MATERIALS AND METHODS:  A total of 40 newly weaned male Wistar albino rats used in the study were randomized into 4 different groups based on the gluten rations they were given. Following 12 weeks of diet they were killed and intracardiac blood samples were collected. Groups were identified as group 1 (n = 10): control group; normal rat ration containing wheat, group 2 (n = 10): gluten-free diet, group 3 (n = 10): ration containing medium level of gluten (normal rat diet+6% vital gluten) and group 4 (n = 10): ration containing high level of gluten (normal rat diet+12% vital gluten). RESULTS:  In groups 3 and 4, high-density lipoprotein was found to be higher than the other 2groups. However, when group 2 results were compared to the other groups; the highest T3, T4, creatinine and B12 levels and the lowest gluten-specific IgE level were observed. alanine aminotransferase and aspartate aminotransferase levels were found to be higher in group 1 compared to the other 3 groups. No statistically significant difference was detected between the groups in terms of other parameters. CONCLUSION:  This study provides evidence that a gluten-containing diet does not cause weight gain, has no diabetogenic effect, and also does not adversely affect general health in relation to hematological, biochemical, and various endocrinological parameters.

Growth response of post weaned F1 Friesian × Borena (Bos taurus × Bos indicus) crossbred growing heifers fed on wheat straw-based densified complete feed block.

This experiment was designed to investigate the effect of feeding wheat-straw based densified complete feed block (DCFB) on daily weight gain, feed intake, digestibility and feed conversion rate in growing heifer calves. Eight weaned F1 Frisian*Borena (Bos taurus × Bos indicus) crossbred calves (92.5 ± 27.5 kg body weight) and 5 months of age were randomly distributed into four groups, each with two animals evaluated under 4 × 4 double Latin Square Design for 240 days. The control treatment was natural pasture hay (NPH) and concentrate mix (CM) fed conventionally in a way that covers 50:50% requirements on dry matter (DM) bases and DCFB prepared by mixing wheat straw (WS) to concentrates mixture in the ratio of 50:50 (T2), 40:60 (T3) and 30:70 (T4), respectively. Each heifer group was fed on each diet for 60 days. At the end of each period the last 7 days were used to collect feed and feacal samples. However, the heifers were weighed each 15 days to estimate daily growth performances. It was found that significant (P < 0.05) differences among groups in average daily gain, feed conversion rate, feed intake and digestibility. The densification of WS and feeding in the form of feed block generally improved feed DM and nutrient intake and digestibility. The increase in the proportion of CM in the DCFBs also increased the DM and nutrient intake and digestibility. Heifer growth rate was higher (P < 0.05) in T1, T3 and T4 diets than T2 groups. Feed conversion ratio was higher (P < 0.05) both in T3 and T4 compared to T1 and T2. The total cost of production per each gram body weight gained was recorded higher (P < 0.05) for calves in the T2 group compared to calves in T1, T3 and T4. In conclusion, maintaining post weaned F1 heifer calves on DCFB composed of wheat straw and a commercial calf's concentrate based diet in the ratio of 40 to 60 would both biologically and economically feasible.

The effects of a diet with high fat content from lard on the health and adipose-markers' mRNA expression in mice.

Pork is one type of the most frequently consumed meat with about 30% globally. Thus, the questions regarding to the health effects of diet with high fat content from lard are raised. Here, we developed a model of mice fed with high fat (HF) from lard to investigate and have more insights on the effects of long-time feeding with HF on health. The results showed that 66 days on HF induced a significant gain in the body weight of mice, and this weight gain was associated to the deposits in the white fat, but not brown fat. The glucose tolerance, not insulin resistance, in mice was decreased by the HF diet, and this was accompanied with significantly higher blood levels of total cholesterol and triglycerides. Furthermore, the weight gains in mice fed with HF seemed to link to increased mRNA levels of adipose biomarkers in lipogenesis, including Acly and Acaca genes, in white fat tissues. Thus, our study shows that a diet with high fat from lard induced the increase in body weight, white fat depots' expansion, disruption of glucose tolerance, blood dyslipidemia, and seemed to start affecting the mRNA expression of some adipose biomarkers in a murine model.

Moringa leaf meal exerts growth benefits in small ruminants through modulating the gastrointestinal microbiome.

This study investigated the impact of feeding 17% moringa leaf meal (MLM) on the ruminal and fecal microbial composition and body weight gain (BWG) performance of lambs (Ovis aries) and kids (Capra hircus). A total of n = 28 lambs (n = 14, no-moringa, n = 14, 17% moringa) and 24 kids (n = 12, no-moringa, n = 12, 17% moringa) were involved in the experiment and body weight was recorded fortnightly. Metagenomic shotgun sequencing was performed on 28, 22, and 26 ruminal solid, liquid fraction, and fecal samples from lambs, and 23, 22, and 23 samples from kids. Moringa supplementation significantly increased BWG in lambs (21.09 ± 0.78 to 26.12 ± 0.81 kg) and kids (14.60 ± 1.29 to 18.28 ± 1.09 kg) (p-value ≤ 0.01). Microbiome analysis revealed an elevated Firmicutes:Bacteroidetes ratio in the moringa diet group. Moringa-fed animals exhibited increased microbial genera associated with volatile fatty acids (VFAs) production (Prevotella, Anaerovibrio, Lachnospiraceae, Butyrivibrio, Christensenella) and starch and fiber digesters (Proteobacteria, Ruminococcus). The increase in the bacterial genus Sharpea suggested possible methane reduction and decreased proportion of pathogens, Aliarcobacter_ID28198, Campylobacter_ID194 and Campylobacter_ID1660076 suggest health benefits. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated significant alterations in microbial gene pool and metabolic pathways related to carbohydrate, protein, lipid and energy metabolism, indicating potential improvements in animal health. Overall, moringa feeding showed higher energy recovery, improved growth, and potential benefits in methane reduction and reduced pathogenic bacteria.

Association of single nucleotide polymorphisms in Neuropeptide Y (NPY) and Phosphoglycerate Mutase 2 (PGAM2) genes with growth traits in rabbits.

Genetic improvement of local rabbit breeds using modern approaches such as marker-assisted selection requires accurate and precise information about marker‒trait associations in animals with different genetic backgrounds. Therefore, this study was designed to estimate the association between two mutations located in the Neuropeptide Y (NPY, g.1778G > C) and Phosphoglycerate Mutase 2 (PGAM2, c.195 C > T) genes in New Zealand White (NZW), Baladi (BR), and V-line rabbits. The first mutation was genotyped using high-resolution melting, and the second mutation was genotyped using the PCR-RFLP method. The results revealed significant associations between the NPY mutation and body weight at 10 (V-line) and 12 weeks of age (NZW, BR, and V-line), body weight gain (BWG) from 10 to 12 weeks of age (BR), BWG from 6 to 12 weeks of age (NZW, BR, and V-line), average daily gain (NZW, BR, and V-line, and BR), growth rate (GR) from 8 to10 weeks (V-line), 10 to 12 weeks (BR), and GR from 6 to 12 weeks of age (BR, and V-line). The PGAM2 mutation was associated with body weight at 10 (V-line) and 12 (NZW, and V-line) weeks of age, with significant positive additive effects at 12 weeks of age in all breeds, and was associated with BWG from 8 to 10 and 10 to 12 in BR, and BWG from 6 to 12 weeks of age (NZW, and BR), and average daily gain (NZW, and BR), and was associated with GR form 8 to 10 weeks (BR), from10 to 12 weeks (BR, and V-line) and from 6 to 12 weeks (BR). The results highlighted the importance of the two mutations in growth development, and the possibility of considering them as candidate genes for late growth in rabbits.

Time-Restricted Feeding Reduces Atherosclerosis in LDLR KO Mice but Not in ApoE Knockout Mice.

BACKGROUND: Dyslipidemia increases cardiovascular disease risk, the leading cause of death worldwide. Under time-restricted feeding (TRF), wherein food intake is restricted to a consistent window of <12 hours, weight gain, glucose intolerance, inflammation, dyslipidemia, and hypercholesterolemia are all reduced in mice fed an obesogenic diet. LDLR (low-density lipoprotein receptor) mutations are a major cause of familial hypercholesterolemia and early-onset cardiovascular disease. METHODS: We subjected benchmark preclinical models, mice lacking LDLR-knockout or ApoE knockout to ad libitum feeding of an isocaloric atherogenic diet either ad libitum or 9 hours TRF for up to 13 weeks and assessed disease development, mechanism, and global changes in hepatic gene expression and plasma lipids. In a regression model, a subset of LDLR-knockout mice were ad libitum fed and then subject to TRF. RESULTS: TRF could significantly attenuate weight gain, hypercholesterolemia, and atherosclerosis in mice lacking the LDLR-knockout mice under experimental conditions of both prevention and regression. In LDLR-knockout mice, increased hepatic expression of genes mediating ß-oxidation during fasting is associated with reduced VLDL (very-low-density lipoprotein) secretion and lipid accumulation. Additionally, increased sterol catabolism coupled with fecal loss of cholesterol and bile acids contributes to the atheroprotective effect of TRF. Finally, TRF alone or combined with a cholesterol-free diet can reduce atherosclerosis in LDLR-knockout mice. However, mice lacking ApoE, which is an important protein for hepatic lipoprotein reuptake do not respond to TRF. CONCLUSIONS: In a preclinical animal model, TRF is effective in both the prevention and regression of atherosclerosis in LDLR knockout mice. The results suggest TRF alone or in combination with a low-cholesterol diet can be a lifestyle intervention for reducing cardiovascular disease risk in humans.

An observational cohort study to investigate the impact of dolutegravir in pregnancy and its obesogenic effects on the metabolic health of women living with HIV and their children: Study protocol.

INTRODUCTION: Dolutegravir (DTG)-based antiretroviral therapy is the World Health Organization's preferred first-line regimen for all persons with HIV, including pregnant women. While DTG has been implicated as an obesogen associated with greater weight gain compared to other antiretrovirals, there is a paucity of data in pregnant women and their children. The Obesogenic oRigins of maternal and Child metabolic health Involving Dolutegravir (ORCHID) study is investigating associations between DTG, weight gain, and metabolic outcomes in the context of HIV. MATERIALS & METHODS: ORCHID is a prospective observational study taking place in Cape Town, South Africa (NCT04991402). A total of 1920 pregnant women with and without HIV infection are being followed from ≤18 weeks gestational age to 24 months postpartum with their children. Participants attend eleven study visits: 3 antenatal, delivery, and 7 postnatal visits. Several embedded sub-studies address specific scientific aims. Primary outcome measurements in mothers include anthropometry, blood pressure, body composition, dysglycemia, insulin resistance (IR), and dyslipidemia. Other maternal measures include demographics, resting energy expenditure, viral load, physical activity, dietary intake, hepatic steatosis, and repository specimens. Sub-study measurements include markers of adipose inflammation, gut integrity, and satiety/hunger, subcutaneous adipose tissue morphology and mitochondrial function, and metabolomics. Primary outcome measurements in children include anthropometry, adipose tissue mass, dysglycemia, IR, and dyslipidemia. Other variables include fetal growth, birth outcomes, medical/breastfeeding history, caloric intake, neurodevelopment, and repository specimens. Sub-study measurements include metabolites/lipid subspecies in umbilical cord blood, as well as breast milk composition and DTG exposure. DISCUSSION: ORCHID will play a pivotal role in defining obesogenic mechanisms and clinical consequences of DTG use in pregnancy in women with HIV and their children. It will provide insights into metabolic disease risk reduction in the context of HIV/DTG, identify intervention targets, and inform public health approaches to diminish chronic metabolic co-morbidities for women and children.

Nutriomic Effects of Precision Lipids on Murine Hepatic Triacylglycerol Alterations Induced by High-Fat Diets.

INTRODUCTION: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. METHODS: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. RESULTS: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. CONCLUSION: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.

Liraglutide for the Treatment of Weight Regain After Bariatric Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

The association between weight change patterns and obesity-related complex multimorbidity: evidence from NHANES.

Objective: Obesity is a major risk factor for non-communicable diseases (NCDs), which has been the leading cause of death nowadays. The aim of this study is to examine the association between total changes in body mass index (BMI) across adulthood and the risk of obesity-related complex multimorbidity in elderly, characterizing the capacity of BMI waves in predicting major chronic diseases. Methods: In this retrospective study, 15,520 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 and 2018. BMI was categorized as obesity (≥30.0 kg/m²), overweight (25.0-29.9 kg/m²), normal weight (18.5-24.9 kg/m²), and underweight (<18.5 kg/m²). Odds ratios (ORs) with 95% confidence interval (CIs) for the relationship between BMI change patterns and major health outcomes included hypertension, cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, and population attributable fractions (PAFs) of BMI were evaluated. Results: In comparison with participants who remained non-obese, those who are stable obese showed the highest risks of developing at least one chronic disease in later life, with odds ratios of 2.76 (95% CI: 2.20 to 3.45) from age 25 years to 10 years before baseline, 2.90 (2.28 to 3.68) from age 25 years to baseline, and 2.49 (2.11 to 2.95) in the 10-year period before baseline. Moving from non-obese to obese weight-change pattern in all periods (from age 25 years to 10 years before baseline: OR = 1.82; 95% CI, 1.57 to 2.11; from age 25 years to baseline: OR = 1.87; 95% CI, 1.59 to 2.19; from 10 years before baseline to baseline: OR = 1.62; 95% CI, 1.26 to 2.08) and moving from obese to non-obese, the 10-year period before baseline (OR = 1.89; 95% CI, 1.39 to 2.57) was associated with increased risk of chronic diseases. Midlife obesity status can explain the 8.6% risk of occurrence of the chronic diseases in elderly. Conclusions: Maintaining a stable healthy weight and losing weight in early adulthood and midlife are important for better life quality during the aging process. More effective strategies and policies to reduce the prevalence of obesity are needed.

Blood pressure increases are associated with weight gain and not antiretroviral regimen or kidney function: a secondary analysis from the ADVANCE trial in South Africa.

INTRODUCTION: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). METHODS: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase-3 trial clinical trial in South Africa (study dates: January 2017-February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment-emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment-emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). RESULTS: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0-3.4), -0.5 mmHg (95% CI: -2.2 to 1.7) and -2.1 mmHg (95% CI: -3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4-22.9), 15.4% (95% CI: 11.0-19.9) and 13.3% (95% CI: 8.9-17.6) of participants developed treatment-emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment-emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. CONCLUSIONS: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment-emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. CLINICAL TRIAL NUMBER: NCT03122262.

Sustained gut dysbiosis and intestinal inflammation show correlation with weight gain in person with chronic HIV infection on antiretroviral therapy.

BACKGROUND: Person with human immunodeficiency virus type-1 (PWH) are prone to chronic inflammation due to residual viral production, even with antiretroviral therapy (ART), which increases the risk of age-related diseases. There is also limited information on changes in the intestinal environment of PWH during ART. In this longitudinal study, we investigated changes in the gut microbiota, persistence of chronic inflammation, interactions between the gut environment and inflammation, and metabolic changes in PWH using long-term ART. RESULTS: We analyzed changes in clinical parameters and gut microbiota in 46 PWH over a mean period of 4 years to understand the influence of gut dysbiosis on inflammation. Overall, changes in the gut microbiota included a decrease in some bacteria, mainly involved in short-chain fatty acid (SCFA) production, and an increase in certain opportunistic bacteria. Throughout the study period, an increase in bacterial-specific metabolic activity was observed in the intestinal environment. Continued decline in certain bacteria belonging to the Clostridia class and metabolic changes in gut bacteria involved in glucose metabolism. Additionally, patients with a low abundance of Parabacteroides exhibited low bacterial alpha diversity and a significant increase in body mass index (BMI) during the study period. Monocyte chemoattractant protein 1, a marker of macrophage activation in the plasma, continued to increase from baseline (first stool collection timepoint) to follow-up (second stool collection timepoint), demonstrating a mild correlation with BMI. Elevated BMI was mild to moderately correlated with elevated levels of plasma interleukin 16 and chemokine ligand 13, both of which may play a role in intestinal inflammation and bacterial translocation within the gut microbiota. The rate of BMI increase correlated with the rate of decrease in certain SCFA-producing bacteria, such as Anaerostipes and Coprococcus 3. CONCLUSION: Our data suggest that despite effective ART, PWH with chronic inflammation exhibit persistent dysbiosis associated with gut inflammation, resulting in a transition to an intestinal environment with metabolic consequences. Moreover, the loss of certain bacteria such as Parabacteroides in PWH correlates with weight gain and may contribute to the development of metabolic diseases.

Rumen and hindgut microbiome regulate average daily gain of preweaning Holstein heifer calves in different ways.

BACKGROUND: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro. RESULTS: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified_g_Pyramidobacter with the rumen metabolites D-fructose (R < - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05). CONCLUSIONS: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract.

Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial.

BACKGROUND: Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. METHODS: Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. RESULTS: Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. CONCLUSIONS: These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03451734.

The metabolic consequences of 'yo-yo' dieting are markedly influenced by genetic diversity.

BACKGROUND: Weight loss can improve the metabolic complications of obesity. However, it is unclear whether insulin resistance persists despite weight loss and whether any protective benefits are preserved following weight regain (weight cycling). The impact of genetic background on weight cycling is undocumented. We aimed to investigate the effects of weight loss and weight cycling on metabolic outcomes and sought to clarify the role of genetics in this relationship. METHOD: Both C57BL/6 J and genetically heterogeneous Diversity Outbred Australia (DOz) mice were alternately fed high fat Western-style diet (WD) and a chow diet at 8-week intervals. Metabolic measures including body composition, glucose tolerance, pancreatic beta cell activity, liver lipid levels and adipose tissue insulin sensitivity were determined. RESULTS: After diet switch from WD (8-week) to chow (8-week), C57BL/6 J mice displayed a rapid normalisation of body weight, adiposity, hyperinsulinemia, liver lipid levels and glucose uptake into adipose tissue comparable to chow-fed controls. In response to the same dietary intervention, genetically diverse DOz mice conversely maintained significantly higher fat mass and insulin levels compared to chow-fed controls and exhibited much more profound interindividual variability than C57BL/6 J mice. Weight cycled (WC) animals were re-exposed to WD (8-week) and compared to age-matched controls fed 8-week WD for the first time (LOb). In C57BL/6 J but not DOz mice, WC animals had significantly higher blood insulin levels than LOb controls. All WC animals exhibited significantly greater beta cell activity than LOb controls despite similar fat mass, glucose tolerance, liver lipid levels and insulin-stimulated glucose uptake in adipose tissue. CONCLUSION: Following weight loss, metabolic outcomes return to baseline in C57BL/6 J mice with obesity. However, genetic diversity significantly impacts this response. A period of weight loss does not provide lasting benefits after weight regain, and weight cycling is detrimental and associated with hyperinsulinemia and elevated basal insulin secretion.