Effect of Protein Intake on Visceral Abdominal Fat and Metabolic Biomarkers in Older Men With Functional Limitations: Results From a Randomized Clinical Trial

Background It remains controversial whether high protein diets improve cardiometabolic profile. We investigated whether increasing protein intake to 1.3 g/kg/day in functionally limited older adults with usual protein intake ≤RDA (0.8 g/kg/day) improves visceral fat accumulation and serum cardiovascular risk markers more than the recommended daily allowance (RDA). Methods The Optimizing Protein Intake in Older Men Trial was a placebo-controlled, randomized trial in which 92 functionally limited men, ≥65 years, with usual protein intake ≤RDA were randomized for 6 months to: 0.8 g/kg/day protein plus placebo; 1.3 g/kg/day protein plus placebo; 0.8 g/kg/day protein plus testosterone enanthate 100 mg weekly; or 1.3 g/kg/day protein plus testosterone enanthate 100 mg weekly. In this substudy, metabolic and inflammatory serum markers were measured in 77 men, and visceral adipose tissue (VAT) was assessed using dual-energy x-ray absorptiometry in 56 men. Results Treatment groups were similar in their baseline characteristics. Randomization to 1.3 g/kg/day protein group was associated with greater reduction in VAT compared to 0.8 g/kg/day group (between-group difference: −17.3 cm2, 95% confidence interval [CI]: −29.7 to −4.8 cm2, p = .008), regardless of whether they received testosterone or placebo. Changes in fasting glucose, fasting insulin, HOMA-IR, leptin, adiponectin, IL-6, and hs-CRP did not differ between the 0.8 versus 1.3 g/kg/day protein groups regardless of testosterone use. Conclusions Protein intake >RDA decreased VAT in functionally limited older men but did not improve cardiovascular disease risk markers. Clinical Trials Registration Number NCT01275365

IL-37 Gene and Cholesterol Metabolism: Association of Polymorphisms with the Presence of Hypercholesterolemia and Cardiovascular Risk Factors. The GEA Mexican Study

Interleukin 37 (IL-37) is an anti-inflammatory cytokine involved in the regulation of cholesterol homeostasis, reducing the levels of plasma cholesterol, fatty acids, and triglycerides. The aim of the present study was to evaluate the association of the IL-37 polymorphisms with the presence of hypercholesterolemia (HC), and with cardiovascular risk factors. Nine IL-37 polymorphisms (rs2708965, rs2708962, rs6717710, rs2708961, rs2708960, rs2708958, rs2723187, rs2708947, and rs2723192) were determined by TaqMan assays in a group of 1292 individuals (514 with and 778 without hypercholesterolemia) belonging to the cohort of the GEA Mexican Study. The associations were evaluated by logistic regression, using inheritance models adjusted by confounding variables. Under codominant 1 model, the rs2708961 (OR = 0.51, p = 0.02), rs2723187 (OR = 0.35, p = 0.005), and rs2708947 (OR = 0.49, p = 0.02) polymorphisms were associated with low risk of HC. The association of the polymorphisms with cardiovascular risk factors was evaluated independently in HC and non-HC individuals. In non-HC individuals, some polymorphisms were associated with the risk of having high levels of LDL-C, glucose, and high risk of T2DM, and low risk of having high visceral abdominal fat. On the other hand, in individuals with HC five, polymorphisms were associated with high levels of C-reactive protein. The IL-37 rs2708961, rs2723187, rs2708947 polymorphisms were associated with low risk of HC, and some IL-37 polymorphisms were associated with cardiometabolic factors in both individuals with and without HC.

Quantification of abdominal fat from computed tomography using deep learning and its association with electronic health records in an academic biobank

Objective The objective was to develop a fully automated algorithm for abdominal fat segmentation and deploy this method at scale and associated with diagnoses in an academic biobank. Materials and Methods We built a fully automated image curation and labeling technique using deep learning and distributive computing to identify subcutaneous and visceral abdominal fat compartments from 47,587 CT scans in 13,422 patients in the Penn Medicine Biobank (PMBB). A classification network identified the inferior and superior borders of the abdomen, and a segmentation network differentiated visceral and subcutaneous fat. Following technical evaluation of our method, we conducted studies to validate known relationships with adiposity. Results When compared with 100 manually annotated cases, the classification network was on average within one 5 mm slice for both the superior (0.3±0.6 slices) and inferior (0.7±0.6 slices) borders. The segmentation network also demonstrated excellent performance with interclass correlation coefficients of 0.99 (p<2e-16) for subcutaneous and 0.99 (p<2e-16) for visceral fat on 100 testing cases. We performed integrative analyses of abdominal fat with the phenome extracted from the electronic health record and found highly significant associations with diabetes mellitus, hypertension, renal failure, among other phenotypes. Conclusion This work presents a fully automated and highly accurate method for the quantification of abdominal fat that can be applied to routine clinical imaging studies to fuel translation scientific discovery.

The role of the gut microbiome in the association between habitual anthocyanin intake and visceral abdominal fat in population-level analysis

ABSTRACT Background Flavonoid intake modifies the composition of the gut microbiome, which contributes to the metabolism of flavonoids. Few studies have examined the contribution of the gut microbiome to the health benefits associated with flavonoid intake. Objectives We aimed to examine associations between habitual intakes of flavonoid subclasses and MRI-determined visceral (VAT) and subcutaneous (SAT) adipose tissue. Uniquely, we also identified associations between the aforementioned measurements and gut microbiome composition sequenced from 16S ribosomal RNA genes. Methods We undertook cross-sectional analyses of 618 men and women (n = 368 male), aged 25–83 y, from the PopGen cohort. Results Higher intake of anthocyanins was associated with lower amounts of VAT [tertile (T)3-T1: −0.49 dm3; β: −8.9%; 95% CI: −16.2%, −1.1%; P = 0.03] and VAT:SAT ratio (T3-T1: −0.04; β: −7.1%; 95% CI: −13.5%, −0.3%; P = 0.03). Higher intakes of anthocyanin-rich foods were also inversely associated with VAT [quantile (Q)4-Q1: −0.39 dm3; β: −9.9%; 95% CI: −17.4%, −1.6%; P = 0.02] and VAT:SAT ratio (Q4-Q1: −0.04; β: −6.5%; 95% CI: −13.3%, −0.9%; P = 0.03). Participants with the highest intakes of anthocyanin-rich foods also had higher microbial diversity (Q4-Q1: β: 0.18; 95% CI: 0.06, 0.31; P &lt; 0.01), higher abundances of Clostridiales (Q4-Q1: β: 449; 95% CI: 96.3, 801; P = 0.04) and Ruminococcaceae (Q4-Q1: β: 313; 95% CI: 33.6, 591; P = 0.04), and lower abundance of Clostridium XIVa (Q4-Q1: β: −41.1; 95% CI: −72.4, −9.8; P = 0.04). Participants with the highest microbial diversity, abundances of Clostridiales and Ruminococcaceae, and lower abundance of Clostridium XIVa had lower amounts of VAT. Up to 18.5% of the association between intake of anthocyanin-rich foods and VAT could be explained by the gut microbiome. Conclusions These novel data suggest that higher microbial diversity and abundance of specific taxa in the Clostridiales order may contribute to the association between higher intake of anthocyanins and lower abdominal adipose tissue.