BCAAs acutely drive glucose dysregulation and insulin resistance: role of AgRP neurons.

BACKGROUND: High-protein diets are often enriched with branched-chain amino acids (BCAAs) known to enhance protein synthesis and provide numerous physiological benefits, but recent studies reveal their association with obesity and diabetes. In support of this, protein or BCAA supplementation is shown to disrupt glucose metabolism while restriction improves it. However, it is not clear if these are primary, direct effects of BCAAs or secondary to other physiological changes during chronic manipulation of dietary BCAAs. METHODS: Three-month-old C57Bl/6 mice were acutely treated with either vehicle/BCAAs or BT2, a BCAA-lowering compound, and detailed in vivo metabolic phenotyping, including frequent sampling and pancreatic clamps, were conducted. RESULTS: Using a catheter-guided frequent sampling method in mice, here we show that a single infusion of BCAAs was sufficient to acutely elevate blood glucose and plasma insulin. While pre-treatment with BCAAs did not affect glucose tolerance, a constant infusion of BCAAs during hyperinsulinemic-euglycemic clamps impaired whole-body insulin sensitivity. Similarly, a single injection of BT2 was sufficient to prevent BCAA rise during fasting and markedly improve glucose tolerance in high-fat-fed mice, suggesting that abnormal glycemic control in obesity may be causally linked to high circulating BCAAs. We further show that chemogenetic over-activation of AgRP neurons in the hypothalamus, as present in obesity, significantly impairs glucose tolerance that is completely normalized by acute BCAA reduction. Interestingly, most of these effects were demonstrated only in male, but not in female mice. CONCLUSION: These findings suggest that BCAAs per se can acutely impair glucose homeostasis and insulin sensitivity, thus offering an explanation for how they may disrupt glucose metabolism in the long-term as observed in obesity and diabetes. Our findings also reveal that AgRP neuronal regulation of blood glucose is mediated through BCAAs, further elucidating a novel mechanism by which brain controls glucose homeostasis.

The association between low carbohydrate diet and odds of metabolic syndrome in adults: A cross-sectional study.

OBJECTIVE: Metabolic syndrome (MetS) has become a major health problem across the globe. Various investigations have been conducted to find the underlying lifestyle-related causes of MetS. Modifiable dietary factors are specifically the center of interest, including the macronutrient composition of the regimen. We aimed to study the association between a low-carbohydrate diet score (LCDS) with MetS and its components in a Kavarian population, located in the center of Iran. METHODS: The present study is a cross-sectional investigation conducted on a healthy sub-sample of PERSIAN Kavar cohort meeting our inclusion criteria (n = 2225). General, dietary, anthropometric, and laboratory data were obtained for each individual using validated questionnaires and measurements. Possible associations between LCDS and MetS and its components were verified using relevant statistical analyses, including analysis of variance and covariance (ANOVA and ANCOVA) and logistic regression. P-values <0.05 were considered as significant. RESULTS: Compared with the lowest LCDS tertiles, those who were assigned to the upper tertiles had lower chance of MetS, after adjusting for potential confounders (OR: 0.66; 95% CI: 0.51-0.85). Moreover, those who assigned to the top LCDS tertile had 23% (OR: 0.77; 95% CI: 0.60-0.98) and 24% (OR: 0.76; 95% CI: 0.60-0.98) lower odds of abdominal adiposity and abnormal glucose homeostasis, respectively. CONCLUSION: We observed a protective effect of low-carbohydrate diet against metabolic syndrome and its components, including abdominal obesity and abnormal glucose homeostasis. However, these initial findings need to be confirmed, especially in the format of clinical trials to ensure causality.

Revisiting the Role of Vitamins and Minerals in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia that affects millions of individuals worldwide. It is an irreversible neurodegenerative disorder that is characterized by memory loss, impaired learning and thinking, and difficulty in performing regular daily activities. Despite nearly two decades of collective efforts to develop novel medications that can prevent or halt the disease progression, we remain faced with only a few options with limited effectiveness. There has been a recent growth of interest in the role of nutrition in brain health as we begin to gain a better understanding of what and how nutrients affect hormonal and neural actions that not only can lead to typical cardiovascular or metabolic diseases but also an array of neurological and psychiatric disorders. Vitamins and minerals, also known as micronutrients, are elements that are indispensable for functions including nutrient metabolism, immune surveillance, cell development, neurotransmission, and antioxidant and anti-inflammatory properties. In this review, we provide an overview on some of the most common vitamins and minerals and discuss what current studies have revealed on the link between these essential micronutrients and cognitive performance or AD.

High Dietary Diabetes Risk Reduction Score Is Associated with Decreased Risk of Chronic Kidney Disease in Tehranian Adults.

Aim: In the current study, we examined the association of dietary diabetes risk reduction score (DDRRS) with chronic kidney disease (CKD) among an Iranian adult population. Methods: We followed up 2076 ≥20-year-old participants of the Tehran Lipid and Glucose Study (2006-2008), who were initially free of CKD for 5.98 years. The dietary diabetes risk reduction score was calculated based on scoring eight components, including cereal fiber, nuts, coffee, polyunsaturated fatty acids-to-saturated fatty acids ratio, glycemic index, sugar-sweetened beverages, trans fatty acids, and red and processed meat using a valid and reliable 168-item food frequency questionnaire. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. A Cox proportional hazard regression model was used to assess the association between the quartiles of DDRRS and CKD incidence. Results: Mean ± SD age of the study population (53% women) was 37.6 ± 12.61 years. During 5.98 years of follow-up, 357 incident cases of CKD were reported. The median (25-75 interquartile range) of DDRRS was 20 (18-22). After adjustment for age, sex, smoking status, total energy intake, body mass index, hypertension, diabetes, eGFR, and physical activity, individuals in the highest versus lowest quartile of DDRRS were 33% less likely to have CKD (HR: 0.67; 95% CI: 0.48-0.96, P for trend: 0.043). Conclusion: The present study's findings suggest that greater adherence to a dietary pattern with a higher score of DDRRS may be associated with a lower risk of CKD incident.

The association between food insecurity and gestational weight gain: A systematic review and meta-analysis.

Gestational weight gain has been one of the most important risk factors for adverse maternal, perinatal, and long-term outcomes. Our systematic review and meta-analysis aimed to incorporate the evidence regarding the association between gestational weight gain and food insecurity (FI). We performed a systematic review and meta-analysis on the possible association between FI and insufficient or excessive gestational weight gain by conducting a systematic search in PubMed, Scopus, ISI, and Google Scholar from January 1, 1990 until February 1, 2022. Odds Ratio (OR) was pooled using a random-effects model. Standard methods were used for the assessment of heterogeneity and publication bias. Data included fifteen studies with 7651 individual participants from different countries pooled for the meta-analysis. Of the fifteen studies included in the final meta-analysis, seven had a cross-sectional and eight had a longitudinal design. In the pooled analysis, FI had significant relationship with both inadequate (OR = 1.49; 95% CI = 1.26 to 1.76) and excessive weight gain in pregnancy (OR = 1.27; 95% CI = 1.05 to 1.54). In conclusion, FI during pregnancy was directly associated with both inadequate and excessive gestational weight gain. Therefore, changes at a policy level should be considered to increase food security in pregnant women.

Mediterranean dietary patterns and risk of type 2 diabetes in the Islamic Republic of Iran.

BACKGROUND: More than 1% of urban Iranians aged >20 years develop type 2 diabetes annually. A major contributing factor is overweight due to energy imbalance and poor quality diet. Even though there are reports on the beneficial effects of some isolated foods on glucose metabolism, researchers are increasingly focusing on dietary patterns versus single foods. AIMS: The aim of this study was to evaluate the association between adherence to a Mediterranean diet and risk of type 2 diabetes. METHODS: The current study was a case-control study nested in the cohort of the Tehran Glucose and Lipid Study. Among participants who met the study criteria, 187 incident cases of diabetes were identified and matched with 374 healthy controls according to sex, age, date of data collection, and previous history of lifestyle intervention. RESULTS: In the highest Mediterranean Diet Scale (MDS) category there were higher intakes of energy, fibre, glycaemic load, carbohydrate, total fat, and olive oil. However saturated fatty acid and monounsaturated fatty acid intakes decreased in higher MDS categories. The multiple adjusted odds ratios (ORs) for type 2 diabetes among individuals with medium (score 3-4) and high (score 5-8) adherence to MDS were 0.79 (95% CI:0.38-1.65) and 0.93 (95% CI:0.44-1.96), respectively, compared to individuals with low adherence (score 0-3). CONCLUSION: Adherence to the Mediterranean dietary pattern was not associated with type 2 diabetes. Increased rates of type 2 diabetes in the Islamic Republic of Iran might be accounted for by the cultural and traditional differences between the Iranian and the Mediterranean dietary patterns.