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Short-Term Effects of Early Menopause on Adiposity, Fatty Acids Profile and Insulin Sensitivity of a Swine Model of Female Obesity.

ABSTRACT: Menopause strongly increases incidence and consequences of obesity and non-communicable diseases in women, with recent research suggesting a very early onset of changes in lipid accumulation, dyslipidemia, and insulin resistance. However, there is a lack of adequate preclinical models for its study. The present trial evaluated the usefulness of an alternative method to surgical ovariectomy, the administration of two doses of a GnRH analogue-protein conjugate (Vacsincel®), for inducing ovarian inactivity in sows used as preclinical models of obesity and menopause. All the sows treated with the compound developed ovarian stoppage after the second dose and, when exposed to obesogenic diets during the following three months, showed changes in the patterns of fat deposition, in the fatty acids profiles at the different tissues and in the plasma concentrations of fructosamine, urea, ?-hydroxibutirate, and haptoglobin when compared to obese fed with the same diet but maintaining ovarian activity. Altogether, these results indicate that menopause early augments the deleterious effects induced by overfeeding and obesity on metabolic traits, paving the way for future research on physiopathology of these conditions and possible therapeutic targets using the swine model.

SUBMITTER: Heras-Molina A

PROVIDER: S-EPMC7565410 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Short-Term Effects of Early Menopause on Adiposity, Fatty Acids Profile and Insulin Sensitivity of a Swine Model of Female Obesity.

Heras-Molina Ana A Pesantez-Pacheco José Luis JL Vazquez-Gomez Marta M Garcia-Contreras Consolacion C Astiz Susana S Isabel Beatriz B Gonzalez-Bulnes Antonio A

Biology 20200911 9

Menopause strongly increases incidence and consequences of obesity and non-communicable diseases in women, with recent research suggesting a very early onset of changes in lipid accumulation, dyslipidemia, and insulin resistance. However, there is a lack of adequate preclinical models for its study. The present trial evaluated the usefulness of an alternative method to surgical ovariectomy, the administration of two doses of a GnRH analogue-protein conjugate (Vacsincel<sup>®</sup>), for inducing ...[more]

PMID: 32932852

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Project description:ContextThere is substantial evidence that reduced short-chain fatty acids (SCFAs) in the gut are associated with obesity and type 2 diabetes, although findings from clinical interventions that can increase SCFAs are inconsistent.ObjectiveThis systematic review and meta-analysis aimed to assess the effect of SCFA interventions on fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR).Data sourcesRelevant articles published up to July 28, 2022, were extracted from PubMed and Embase using the MeSH (Medical Subject Headings) terms of the defined keywords [(short-chain fatty acids) AND (obesity OR diabetes OR insulin sensitivity)] and their synonyms. Data analyses were performed independently by two researchers who used the Cochrane meta-analysis checklist and the PRISMA guidelines.Data extractionClinical studies and trials that measured SCFAs and reported glucose homeostasis parameters were included in the analysis. Standardized mean differences (SMDs) with 95%CIs were calculated using a random-effects model in the data extraction tool Review Manager version 5.4 (RevMan 5.4). The risk-of-bias assessment was performed following the Cochrane checklist for randomized and crossover studies.Data analysisIn total, 6040 nonduplicate studies were identified, 23 of which met the defined criteria, reported fasting insulin, fasting glucose, or HOMA-IR values, and reported change in SCFA concentrations post intervention. Meta-analyses of these studies indicated that fasting insulin concentrations were significantly reduced (overall effect: SMD = -0.15; 95%CI = -0.29 to -0.01, P = 0.04) in treatment groups, relative to placebo groups, at the end of the intervention. Studies with a confirmed increase in SCFAs at the end of intervention also had a significant effect on lowering fasting insulin (P = 0.008). Elevated levels of SCFAs, compared with baseline levels, were associated with beneficial effects on HOMA-IR (P < 0.00001). There was no significant change in fasting glucose concentrations.ConclusionIncreased postintervention levels of SCFAs are associated with lower fasting insulin concentrations, offering a beneficial effect on insulin sensitivity.Systematic review registrationPROSPERO registration number CRD42021257248.

Project description:Background/objectivesHigh dietary fibre intakes may protect against obesity by influencing colonic fermentation and the colonic microbiota. Though, recent studies suggest that increased colonic fermentation contributes to adiposity. Diet influences the composition of the gut microbiota. Previous research has not evaluated dietary intakes, body mass index (BMI), faecal microbiota and short chain fatty acid (SCFA) in the same cohort. Our objectives were to compare dietary intakes, faecal SCFA concentrations and gut microbial profiles in healthy lean (LN, BMI⩽25) and overweight or obese (OWOB, BMI>25) participants.DesignWe collected demographic information, 3-day diet records, physical activity questionnaires and breath and faecal samples from 94 participants of whom 52 were LN and 42 OWOB.ResultsDietary intakes and physical activity levels did not differ significantly between groups. OWOB participants had higher faecal acetate (P=0.05), propionate (P=0.03), butyrate (P=0.05), valerate (P=0.03) and total short chain fatty acid (SCFA; P=0.02) concentrations than LN. No significant differences in Firmicutes to Bacteroides/Prevotella (F:B) ratio was observed between groups. However, in the entire cohort, Bacteroides/Prevotella counts were negatively correlated with faecal total SCFA (r=-0.32, P=0.002) and F:B ratio was positively correlated with faecal total SCFA (r=0.42, P<0.0001). Principal component analysis identified distinct gut microbiota and SCFA-F:B ratio components, which together accounted for 59% of the variation. F:B ratio loaded with the SCFA and not with the microbiota suggesting that SCFA and F:B ratio vary together and may be interrelated.ConclusionsThe results support the hypothesis that colonic fermentation patterns may be altered, leading to different faecal SCFA concentrations in OWOB compared with LN humans. More in-depth studies looking at the metabolic fate of SCFA produced in LN and OWOB participants are needed in order to determine the role of SCFA in obesity.

Project description:Postural orthostatic tachycardia syndrome (POTS) is a devastating chronic form of orthostatic intolerance associated with excessive heart rate increase without hypotension during upright posture. POTS patients exhibit increased circulating norepinephrine levels with exaggerated sympathetic nervous system response upon standing. Emerging evidence suggests a role for the gut microbiome in cardiovascular disorders. However, the etiology of POTS and whether the gut microbiome plays a role are not fully elucidated. We assessed whether the gut microbiome and fecal short-chain fatty acids were different in POTS patients (N = 25) compared to healthy control (N = 23) women. Patients underwent hemodynamic measurements while supine and upon standing. Fecal samples were collected and analyzed using shotgun sequencing and Liquid Chromatography-High Resolution Mass Spectrometry and dietary habits were measured with a fitness application. We found that POTS patients in the standing position had higher circulating norepinephrine and epinephrine levels and increased heart rate. There were no differences in diet composition between groups. Of note dietary salt intake was also similar despite the fact that these patients are advised to consume a high salt diet. Alpha and beta diversity were similar between groups. We observed no differences in bacteria at the phylum levels or Firmicutes to Bacteroidetes ratio. We found no significant differences at the genus level, but observed trends in certain bacteria. Lachnoclostridium genus were higher in POTS when compared to the control group. On the other hand, Coprococcus and Coprobacter, were lower in POTS patients compared to controls. Although our KEGG metabolic pathways indicated differences related to short-chain fatty acids (SCFAs), we found that both POTS patients and healthy controls had similar levels of SCFAs. These results suggest POTs per se may have limited effects on gut microbiota composition and derived SCFAs. Further studies are needed to assess the role of the alterations observed at the genus level.

Dataset Information

Short-Term Effects of Early Menopause on Adiposity, Fatty Acids Profile and Insulin Sensitivity of a Swine Model of Female Obesity.

Publications

Short-Term Effects of Early Menopause on Adiposity, Fatty Acids Profile and Insulin Sensitivity of a Swine Model of Female Obesity.

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