The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Obesity is a multifaceted disease characterized by an abnormal accumulation of adipose tissue. Growing evidence has proposed microbiota-derived metabolites as a potential factor in the pathophysiology of obesity and related metabolic conditions over the last decade. As one of the essential metabolites, butyrate affects several host cellular mechanisms related to appetite sensations and weight control. However, the effects of butyrate on obesity in humans have yet to be studied. Thus, the present study was aimed to evaluate the effects of sodium butyrate (SB) supplementation on the expression levels of peroxisome proliferator activated-receptor (PPAR) gamma coactivator-1α (PGC-1α), PPARα and uncoupling protein 1 (UCP1) genes, serum level of glucagon-like peptide (GLP1), and metabolic parameters, as well as anthropometric indices in obese individuals on a weight loss diet. METHODS: This triple-blind randomized controlled trial (RCT) will include 50 eligible obese subjects aged between 18 and 60 years. Participants will be randomly assigned into two groups: 8 weeks of SB (600 mg/day) + hypo-caloric diet or placebo (600 mg/day) + hypo-caloric diet. At weeks 0 and 8, distinct objectives will be pursued: (1) PGC-1α, PPARα, and UCP1 genes expression will be evaluated by real-time polymerase chain reaction; (2) biochemical parameters will be assayed using enzymatic methods; and (3) insulin and GLP1 serum level will be assessed by enzyme-linked immunosorbent assay kit. DISCUSSION: New evidence from this trial may help fill the knowledge gap in this realm and facilitate multi-center clinical trials with a substantially larger sample size. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20190303042905N2 . Registered on 31 January 2021.

Mechanistic insights into the pleiotropic effects of butyrate as a potential therapeutic agent on NAFLD management: A systematic review.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases worldwide. As a multifaceted disease, NAFLD's pathogenesis is not entirely understood, but recent evidence reveals that gut microbiota plays a significant role in its progression. Butyrate, a gut microbiota metabolite, has been reported to have hepato-protective effects in NAFLD animal models. The purpose of this systematic review is to determine how butyrate affects the risk factors for NAFLD. Searches were conducted using relevant keywords in electronic databases up to March 2022. According to the evidence presented in this study, butyrate contributes to a wide variety of biological processes in the gut-liver axis. Its beneficial properties include improving intestinal homeostasis and liver health as well as anti-inflammatory, metabolism regulatory and anti-oxidative effects. These effects may be attributed to butyrate's ability to regulate gene expression as an epigenetic modulator and trigger cellular responses as a signalling molecule. However, the exact underlying mechanisms remain unclear. Human trials have not been performed on the effect of butyrate on NAFLD, so there are concerns about whether the results of animal studies can be translated to humans. This review summarises the current knowledge about the properties of butyrate, particularly its potential effects and mechanisms on liver health and NAFLD management.

Associations between new and old anthropometric indices with type 2 diabetes mellitus and risk of metabolic complications: a cross-sectional analytical study.

BACKGROUND: Obesity can increase the risk of diabetes mellitus and complications associated with it. OBJECTIVES: The aim of this study was to estimate the associations between new and old anthropometric indices and the risk of type 2 diabetes mellitus (T2DM) and its metabolic complications. METHODS: In this cross-sectional analytical study, 110 T2DM subjects and 110 healthy controls were selected by convenience sampling. Metabolic factors were evaluated including the atherogenic index of plasma (AIP), glycemic status, lipid profile, blood pressure, kidney indices, new anthropometric indices (abdominal volume index [AVI], body shape index [ABSI], lipid accumulation product [LAP], body adiposity index [BAI], and conicity index [CI]), and old anthropometric indices (weight, body mass index [BMI], and waist and hip circumference [WC and HC]). RESULTS: Significant positive correlations were observed between AVI, LAP, and BAI and fasting blood glucose and HbA1c in the T2DM group (p < 0.001 for all associations). The odds ratio (OR) for T2DM elevated significantly with increasing BMI (OR: 1.30, 95% CI: 1.20-1.42), LAP (OR: 1.20, 95% CI: 1.13-1.27), and BAI (OR: 1.32, 95% CI: 1.21-1.43). The indices AVI (OR: 1.90, 95% CI: 1.57-2.29), LAP (OR: 1.19, 95% CI: 1.13-1.27), BAI (OR: 1.19, 95% CI: 1.12-1.26), WC (OR: 1.29, 95% CI: 1.18, 1.42), and HC (OR: 1.07, 95% CI: 1.01, 1.14) significantly increased the risk of metabolic syndrome (MetS). CONCLUSIONS: Associations were identified between obesity indices and diabetes. These indices could be used in clinical practice for evaluation and control of T2DM.

CONTEXTO: A obesidade pode aumentar o risco de diabetes melito e complicações associadas. OBJETIVOS: O objetivo deste estudo foi estimar a associação de índices antropométricos novos e antigos com o risco de diabetes melito tipo 2 (DM2) e suas complicações metabólicas. MÉTODOS: Neste estudo analítico transversal, 110 indivíduos com DM2 e 110 controles saudáveis foram selecionados por amostragem de conveniência. Foram avaliados os fatores metabólicos, incluindo índice aterogênico plasmático, estado glicêmico, perfil lipídico, pressão arterial, índices renais, índices antropométricos novos [índice de volume abdominal (AVI), índice de formato corporal (ABSI), produto de acumulação lipídica (LAP), índice de adiposidade corporal (BAI) e índice de conicidade (CI)] e índices antropométricos antigos [peso, índice de massa corporal (IMC), circunferência de cintura e quadril]. RESULTADOS: Foi observada uma correlação positiva significativa de AVI, LAP e BAI com glicemia de jejum e hemoglobina glicada no grupo DM2 (p para todos < 0,001). A odds ratio (OR) do grupo DM2 foi significativamente elevada com aumento de IMC [OR: 1,30, intervalo de confiança (IC) de 95%: 1,20-1,42], LAP (OR: 1,20, IC95%: 1,13-1,27) e BAI (OR: 1,32, IC95%: 1,21-1,43). Os índices AVI (OR: 1,90, IC95%: 1,57-2,29), LAP (OR: 1,19, IC95%: 1,13-1,27), BAI (OR: 1,19, IC95%: 1,12-1,26), WC (OR: 1,29, IC95%: 1,18-1,42) e HC (OR: 1,07, IC95%: 1,01-1,14) aumentaram significativamente o risco de síndrome metabólica. CONCLUSÕES: Foi reconhecida uma associação entre índices de obesidade e diabetes. Esses índices podem ser usados na prática clínica para avaliação e controle do DM2.

Consumption of melatonin supplement improves cardiovascular disease risk factors and anthropometric indices in type 2 diabetes mellitus patients: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Diabetes mellitus is a common chronic disease. Dyslipidemia and hypertension are two complications that may develop in diabetic patients if hyperglycemia, insulin resistance, and weight gain are not controlled. This study investigated the effects of melatonin supplementation on some cardiovascular disease risk factors and anthropometric indices in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 50 T2DM patients were randomly allocated to intervention and control groups which received two tablets of either melatonin or placebo (250 mg) once a day for 8 weeks. Systolic blood pressure (SBP), mean arterial pressure (MAP), pulse pressure (PP), the atherogenic index of plasma (AIP), weight, body mass index (BMI), waist and hip circumference (WC, HC), a body shape index (ABSI), abdominal volume index (AVI), body adiposity index (BAI), lipid accumulation product (LAP), conicity index, and waist-to-height ratio (WHtR) were evaluated in all the patients pre- and post-intervention. RESULTS: Melatonin supplementation for 8 weeks significantly decreased the mean levels of SBP, MAP, PP, weight, BMI, WC, HC, BAI, AVI, conicity index, and WHtR post-intervention (p <  0.05). Also, the median changes of SBP, MAP, PP, weight, BMI, WC, HC BAI, AVI, and conicity index were significantly lower in the intervention group compared with the control group (p <  0.05). A significant increase (p <  0.001) was observed in the mean levels of ABSI in the intervention group. The median changes of ABSI were significantly greater in the intervention group compared with the control group (p <  0.001). CONCLUSIONS: Consumption of melatonin supplement may be effective in controlling arterial pressure including SBP, MAP, and PP and anthropometric indices (as predictors of obesity) in T2DM patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20190303042905N1 . Registered on 17 May 2019.

Role of Butyrate, a Gut Microbiota Derived Metabolite, in Cardiovascular Diseases: A comprehensive narrative review.

Cardiovascular diseases (CVD) are major causes of death worldwide. Recently, new roles for intestinal microbiota in pathology and treatment of CVD have been proposed. Butyrate, a bacterial metabolite, is synthesized in the gut and performs most of its functions in there. However, researchers have discovered that butyrate could enter to portal vein and interact with various organs. Butyrate exhibits a broad range of pharmacological activities, including microbiome modulator, anti-inflammatory, anti-obesity, metabolic pathways regulator, anti-angiogenesis, and antioxidant. In this article we review evidence supporting a potentially therapeutic role for butyrate in CVD and the mechanisms and pathways involved in the cardio-protective effects of butyrate from the gut and circulation to the nervous system. In summary, although butyrate exhibits a wide variety of biological activities in different pathways including energy homeostasis, glucose and lipid metabolism, inflammation, oxidative stress, neural signaling, and epigenetic modulation in experimental settings, it remains unclear whether these findings are clinically relevant and whether the molecular pathways are activated by butyrate in humans.

Associations between new and old anthropometric indices with type 2 diabetes mellitus and risk of metabolic complications: a cross-sectional analytical study / Associação de índices antropométricos novos e antigos com diabetes melito tipo 2 e risco de complicações metabólicas: um estudo analítico de corte transversal

Abstract Background Obesity can increase the risk of diabetes mellitus and complications associated with it. Objectives The aim of this study was to estimate the associations between new and old anthropometric indices and the risk of type 2 diabetes mellitus (T2DM) and its metabolic complications. Methods In this cross-sectional analytical study, 110 T2DM subjects and 110 healthy controls were selected by convenience sampling. Metabolic factors were evaluated including the atherogenic index of plasma (AIP), glycemic status, lipid profile, blood pressure, kidney indices, new anthropometric indices (abdominal volume index [AVI], body shape index [ABSI], lipid accumulation product [LAP], body adiposity index [BAI], and conicity index [CI]), and old anthropometric indices (weight, body mass index [BMI], and waist and hip circumference [WC and HC]). Results Significant positive correlations were observed between AVI, LAP, and BAI and fasting blood glucose and HbA1c in the T2DM group (p < 0.001 for all associations). The odds ratio (OR) for T2DM elevated significantly with increasing BMI (OR: 1.30, 95% CI: 1.20-1.42), LAP (OR: 1.20, 95% CI: 1.13-1.27), and BAI (OR: 1.32, 95% CI: 1.21-1.43). The indices AVI (OR: 1.90, 95% CI: 1.57-2.29), LAP (OR: 1.19, 95% CI: 1.13-1.27), BAI (OR: 1.19, 95% CI: 1.12-1.26), WC (OR: 1.29, 95% CI: 1.18, 1.42), and HC (OR: 1.07, 95% CI: 1.01, 1.14) significantly increased the risk of metabolic syndrome (MetS). Conclusions Associations were identified between obesity indices and diabetes. These indices could be used in clinical practice for evaluation and control of T2DM.

Resumo Contexto A obesidade pode aumentar o risco de diabetes melito e complicações associadas. Objetivos O objetivo deste estudo foi estimar a associação de índices antropométricos novos e antigos com o risco de diabetes melito tipo 2 (DM2) e suas complicações metabólicas. Métodos Neste estudo analítico transversal, 110 indivíduos com DM2 e 110 controles saudáveis foram selecionados por amostragem de conveniência. Foram avaliados os fatores metabólicos, incluindo índice aterogênico plasmático, estado glicêmico, perfil lipídico, pressão arterial, índices renais, índices antropométricos novos [índice de volume abdominal (AVI), índice de formato corporal (ABSI), produto de acumulação lipídica (LAP), índice de adiposidade corporal (BAI) e índice de conicidade (CI)] e índices antropométricos antigos [peso, índice de massa corporal (IMC), circunferência de cintura e quadril]. Resultados Foi observada uma correlação positiva significativa de AVI, LAP e BAI com glicemia de jejum e hemoglobina glicada no grupo DM2 (p para todos < 0,001). A odds ratio (OR) do grupo DM2 foi significativamente elevada com aumento de IMC [OR: 1,30, intervalo de confiança (IC) de 95%: 1,20-1,42], LAP (OR: 1,20, IC95%: 1,13-1,27) e BAI (OR: 1,32, IC95%: 1,21-1,43). Os índices AVI (OR: 1,90, IC95%: 1,57-2,29), LAP (OR: 1,19, IC95%: 1,13-1,27), BAI (OR: 1,19, IC95%: 1,12-1,26), WC (OR: 1,29, IC95%: 1,18-1,42) e HC (OR: 1,07, IC95%: 1,01-1,14) aumentaram significativamente o risco de síndrome metabólica. Conclusões Foi reconhecida uma associação entre índices de obesidade e diabetes. Esses índices podem ser usados na prática clínica para avaliação e controle do DM2.

Association of proinflammatory genes expression with serum interleukin 1ß and free fatty acids in metabolically healthy and unhealthy abdominally obese individuals: a case-control study.

BACKGROUND: Proinflammatory genes are highly expressed in several metabolic disorders associated with obesity. But it is not clarified whether gene expression levels and downstream inflammatory markers are related to the metabolic state or the presence of obesity. Hence, the present study aimed to compare Toll-Like Receptor 2 (TLR2), Myeloid Differentiation Factor 88 (MyD88), and NFĸB mRNA expression levels between metabolically healthy abdominally obese (MHAO) and metabolically unhealthy abdominally obese (MUAO) individuals. RESULTS: We compared mRNA expression levels of the genes as well as serum FFAs and IL-1ß in MUAO (n = 36) and MHAO (n = 34) groups. Serum FBS, TG, and HDL-C in addition to systolic and diastolic blood pressure were significantly higher in MUAO than MHAO groups (p < 0.05). The odds of MUAO was significantly decreased with high HDL-C (OR = 0.22, 95%CI: 0.08-0.63) and increased with high FBS (OR = 7.04, 95%CI: 1.42-34.69) and TG (OR = 30.55, 95%CI: 7.48-60.67). There were no significant differences in proinflammatory genes as well as serum FFAs and IL-1ß between the two groups. No associations were found between the genes expression and serum markers. However, NFĸB expression was significantly correlated with TLR2 and MyD88 (r = 0.747; p < 0.001). Significant correlations were also noticed between TLR2 and MyD88 expression as well as between serum FFAs and IL-1ß in each group (p < 0.001). CONCLUSION: Serum concentration of IL-1ß, FFAs, and mRNA expression levels of TLR2, MyD88, and NFĸB may be resulted from abdominal obesity and not be related to the presence or absence of metabolic health.

Inflammatory Potential of Diet: Association With Chemerin, Omentin, Lipopolysaccharide-Binding Protein, and Insulin Resistance in the Apparently Healthy Obese.

OBJECTIVE: Low-grade inflammation is a characteristic of various conditions, including obesity. Diet is regarded as a strong modifier of inflammation. The potential links between inflammatory properties of diet and adipokines as well as insulin resistance (IR) warrant further investigation. Therefore, this study aimed to examine the associations of the dietary inflammatory index (DII) with serum chemerin, omentin, and lipopolysaccharide-binding protein (LBP) as well as IR among apparently healthy obese adults. DESIGN: In this cross-sectional study, 171 abdominally obese subjects were recruited in the northwest of Iran. Demographic data, dietary intake, anthropometric indices, and physical activity (PA) were assessed. DII scores were calculated based on dietary intake, using a validated 168-item food frequency questionnaire (FFQ). Basal blood samples were collected to determine the biochemical parameters. A linear regression test with adjusted beta estimates was applied for data analysis. RESULT: Compared to those with higher DII score, the group with lower DII score (anti-inflammatory diet) had higher protein (83.62 ± 36.42 g vs. 71.61 ± 25.94 g) and lower carbohydrate (325.00 ± 125.76 g vs. 378.19 ± 137.69 g) intake. Participants with higher DII score had lower consumption of polyunsaturated and monounsaturated fats as well as fiber and higher saturated fats (p < .001). Those with elevated DII score had higher levels of chemerin (p = .034) and LBP (p = .040), compared to those with lower DII. Omentin showed no significant differences between groups with different DII scores. Additionally, people with a more proinflammatory diet had higher FBS (p = .005); however, other markers of IR did not differ by DII scores. CONCLUSIONS: The results suggest that increased inflammatory potential of diet, as indicated by higher DII score, is associated with elevated levels of chemerin and LBP. While DII was positively associated with FBS, no significant correlation was found for insulin and other indices of IR.

Toll-like receptor signaling and serum levels of interferon ß and lipopolysaccharide binding protein are related to abdominal obesity: a case-control study between metabolically healthy and metabolically unhealthy obese individuals.

It is still unclear whether toll-like receptor (TLR) signaling and serum levels of inflammatory markers in metabolically unhealthy abdominally obese (MUAO) are due to their obesity and/or their metabolic state. We hypothesized that abdominal obesity is an important mediator of the association of metabolic state with TLR signaling and serum inflammatory markers. Therefore, in this case-control study, we compared the expression levels of TLR4 and Toll/interleukin-1 receptor domain containing adaptor protein-inducing interferon ß (TRIF) and serum concentrations of interferon ß and lipoprotein-binding protein (LBP) in metabolically healthy abdominally obese (MHAO) and MUAO individuals. Basal blood samples from 65 abdominally obese subjects with waist circumference (WC) of at least 95 cm were collected to determine serum metabolic parameters, IFNß, and LBP. Those with 3 or more metabolic alterations were defined as MUAO (n = 34), and those having 2 or less were classified as MHAO (n = 31). Furthermore, messenger RNA (mRNA) was isolated from peripheral blood mononuclear cells. TLR4 and TRIF gene expression assay was performed using quantitative real-time polymerase chain reaction. There were significant differences in serum fasting blood sugar (P = .017), triglyceride (P < .001), cholesterol (P = .002), and low-density lipoprotein cholesterol (P = .034) between the MUAO and MHAO groups, whereas no significant difference was observed in the expression ratio of TLR4 and TRIF mRNA and serum levels of IFNß and LBP. However, a significant correlation was noticed between mRNA expression levels of TLR4 and TRIF (r = 0.50, P < .001) and serum IFNß and LBP (r = 0.70, P < .001). It is concluded that the expression levels of TLR4 and TRIF as well as serum IFNß and LBP are more related to abdominal obesity than to metabolic health.

Association of endotoxaemia with serum free fatty acids in metabolically healthy and unhealthy abdominally obese individuals: a case-control study in northwest of Iran.

OBJECTIVES: This study aimed to compare serum free fatty acids (FFAs) and lipopolysaccharide-binding protein (LBP) between metabolically healthy abdominally obese (MHAO) and metabolically unhealthy abdominally obese (MUAO) individuals. We also examined the association between serum FFAs and LBP in the participants. METHODS: In this age-matched and gender-matched case-control study, 164 abdominally obese subjects were recruited from June to November 2015 in the northwest of Iran. Demographic data, dietary intake, body composition, anthropometric indices and physical activity (PA) were assessed. Basal blood samples were collected to determine serum metabolic parameters, FFAs and LBP. Abdominal obesity was defined as having waist circumference ≥95 cm. Those with three or more metabolic alterations were defined as MUAO and those having two or less were classified as MHAO. Data were analysed using SPSS V.17.0. RESULTS: There were no significant differences in dietary intake, anthropometric indices, body composition and PA between the two groups. The odds of MUAO significantly increased by increments in serum fasting blood sugar (OR 3.79, 95% CI 2.25 to 6.40), triglycerides (OR 1.10, 95% CI 1.05 to 1.15), systolic blood pressure (OR 1.02, 95% CI 1.00 to 1.04) and diastolic blood pressure (OR 1.03, 95% CI 1.01 to 1.06) and decreased by increase in serum high-density lipoprotein cholesterol (OR 0.32, 95% CI 0.20 to 0.52). The levels of LBP and FFAs showed no significant differences between the two groups. However, significant correlations were found between LBP and FFAs in pooled population (r=0.712; p<0.001) as well as in cases (r=0.717; p<0.001) and controls (r=0.704; p<0.001). Neither FFAs nor LBP were significantly correlated with dietary intake or metabolic parameters (p>0.05). CONCLUSION: The results indicated that serum LBP and FFAs are highly correlated both in MHAO and MUAO states. In addition, the levels of LBP and FFAs seem to be more related to abdominal obesity than to the presence or absence of metabolic health.