Finkelstein, O., G. Levakov, A. Kaplan, H. Zelicha, A.Y. Meir, E. Rinott, G. Tsaban, A.V. Witte, M. Blüher, M. Stumvoll, I. Shelef, I. Shai, T. Riklin Raviv, G. Avidan, 2024. Deep learning-based BMI inference from structural brain MRI reflects brain alterations following lifestyle intervention. Hum Brain Mapp. 45(3):e26595. doi: 10.1002/hbm.26595.
Obesity is associated with negative effects on the brain. We exploit Artificial Intelligence (AI) tools to explore whether differences in clinical measurements following lifestyle interventions in overweight population could be reflected in brain morphology. In the DIRECT-PLUS clinical trial, participants with criterion for metabolic syndrome underwent an 18-month lifestyle intervention. Structural brain MRIs were acquired before and after the intervention. We utilized an ensemble learning framework to predict Body-Mass Index (BMI) scores, which correspond to adiposity-related clinical measurements from brain MRIs. We revealed that patient-specific reduction in BMI predictions was associated with actual weight loss and was significantly higher in active diet groups compared to a control group. Moreover, explainable AI (XAI) maps highlighted brain regions contributing to BMI predictions that were distinct from regions associated with age prediction. Our DIRECT-PLUS analysis results imply that predicted BMI and its reduction are unique neural biomarkers for obesity-related brain modifications and weight loss.
Key Area: Body Weight & Composition
Sumislawski, K., A. Widmer, R.R. Suro, M.E. Robles, K. Lillegard, D. Olson, J.R. Koethe, H.J. Silver, 2023. Consumption of tree nuts as snacks reduces metabolic syndrome risk in young adults: a randomized trial. Nutrients. 15(24):5051. doi: 10.3390/nu15245051.
Metabolic syndrome (MetSx) and its chronic disease consequences are major public health concerns worldwide. Between-meal snacking may be a modifiable risk factor. We hypothesized that consuming tree nuts as snacks, versus typical carbohydrate snacks, would reduce risk for MetSx in young adults. A prospective, randomized, 16-week parallel-group diet intervention trial was conducted in 84 adults aged 22-36 with BMI 24.5 to 34.9 kg/m2 and ≥1 MetSx clinical risk factor. Tree nuts snacks (TNsnack) were matched to carbohydrate snacks (CHOsnack) for energy (kcal), protein, fiber, and sodium content as part of a 7-day eucaloric menu. Difference in change between groups was tested by analysis of covariance using general linear models. Multivariable linear regression modeling assessed main effects of TNsnack treatment and interactions between TNsnack and sex on MetSx score. Age, BMI, and year of study enrollment were included variables. There was a main effect of TNsnack on reducing waist circumference in females (mean difference: -2.20 ± 0.73 cm, p = 0.004) and a trend toward reduced visceral fat (-5.27 ± 13.05 cm2, p = 0.06). TNsnack decreased blood insulin levels in males (-1.14 ± 1.41 mIU/L, p = 0.05) and multivariable modeling showed a main effect of TNsnack on insulin. Main effects of TNsnack on triglycerides and TG/HDL ratio were observed (p = 0.04 for both) with TG/HDL ratio reduced ~11%. A main effect of TNsnack (p = 0.04) and an interaction effect between TNsnack and sex (p < 0.001) on total MetSx score yielded 67% reduced MetSx score in TNsnack females and 42% reduced MetSx score in TNsnack males. To our knowledge, this is the first randomized parallel-arm study to investigate cardiometabolic responses to TNsnacks versus typical CHOsnacks among young adults at risk of MetSx. Our study suggests daily tree nut consumption reduces MetSx risk by improving waist circumference, lipid biomarkers, and/or insulin sensitivity-without requiring caloric restriction.
Gao, P., E. Rinott, D. Dong, Z. Mei, F. Wang, Y. Liu, O. Kamer, A. Yaskolka Meir, K.M. Tuohy, M. Blüher, M. Stumvoll, M.J. Stampfer, I. Shai, D.D. Wang, 2024. Gut microbial metabolism of bile acids modifies the effect of Mediterranean diet interventions on cardiometabolic risk in a randomized controlled trial. Gut Microbes. 16(1):2426610. doi: 10.1080/19490976.2024.2426610.
Bile acids (BAs) undergo extensive microbial metabolism in the gut and exert hormone-like functions on physiological processes underlying metabolic risk. However, the extent to which gut BA profiles predict cardiometabolic risk and explain individual responses to dietary interventions in humans is still unclear. In the DIRECT-PLUS Trial, we conducted a multi-omics analysis of 284 participants randomized into three groups: healthy dietary guidelines and two Mediterranean diet (MedDiet) groups. We longitudinally measured 44 fecal BAs using liquid chromatography-mass spectrometry, the gut microbiome through shotgun metagenomic sequencing, and body adiposity and serum lipids at baseline, 6, and 18 months. Fecal levels of 14 BAs, such as lithocholic acid and ursodeoxycholic acid, were prospectively associated with body mass index (BMI) and serum lipid profiles (false discovery rate [q]<0.05). Baseline fecal BA levels significantly modified the beneficial effects of the MedDiet; for example, BMI reduction induced by MedDiet interventions was more pronounced in individuals with lower 12-dehydrocholic acid levels (q-interaction <0.001). We confirmed that the gut microbiome is a major modifier of the secondary BA pool in humans. Furthermore, the association of fecal BAs with body adiposity and serum lipids varied significantly in individuals with different abundances of gut microbes carrying BA metabolism enzymes, e.g. several Ruminococcus spp. In summary, our study identifies novel predictive biomarkers for cardiometabolic risk and offers new mechanistic insights to guide personalized dietary interventions.
Lopez-Neyman, S. M., N. Zohoori, K.S. Broughton, D.C. Miketinas, 2023. Association of tree nut consumption with cardiovascular disease and cardiometabolic risk factors and health outcomes in US adults: NHANES 2011-2018. Curr. Dev. Nutr. 7(10):102007. https://doi.org/10.1016/j.cdnut.2023.102007
Background: Tree nuts are nutrient dense, and their consumption has been associated with improvements in health outcomes. Objective: To estimate the usual tree nut intake and examine the association between tree nut consumption and cardiometabolic (CM) health outcomes in a nationally representative sample of US adults. Methods: Cross-sectional data were analyzed from a sample of 18,150 adults aged ≥ 20y who provided at least one reliable 24-h dietary recall and had complete data for the variables of interest in the NHANES 2011-2018. Tree nut consumers were defined as those consuming ≥ ¼ ounce/d (7.09 g). The National Cancer Institute Method was used to estimate the usual tree nut intake among consumers. Measurement error calibrated regression models were used to assess the association between tree nut consumption and each health outcome of interest. Results: Approximately 8% of all participants (n = 1238) consumed tree nuts and had a mean ± SE usual intake of 39.5 ± 1.8 g/d. Tree nut consumers were less likely to have obesity (31% vs. 40%, P < 0.001) and low high-density lipoprotein cholesterol (22% vs. 30%, P < 0.001) compared with nonconsumers. Moreover, tree nut consumers had a lower mean waist circumference (WC) (97.1 ± 0.7 vs. 100.5 ± 0.3 cm, P < 0.001) and apolipoprotein B (87.5 ± 1.2 vs. 91.8 ± 0.5 mg/dL, P = 0.004) than nonconsumers. After adjusting models for demographics and lifestyle covariates, the difference in WC between average intake (33.7 g/d) and low threshold intake (7.09/g) of tree nuts was -1.42 ± 0.58 cm (P = 0.005). Conclusions: Most US adults do not consume tree nuts, yet modest consumption was associated with decreased prevalence of cardiovascular disease and CM risk factors and improvement for some health outcome measures.
