SUMMARY The mammalian brain is composed of thousands of interacting neural cell types. Systematic approaches to establish the molecular identity of functional populations of neurons would advance our understanding of neural mechanisms controlling behavior. Here, we show that ribosomal protein S6, a structural component of the ribosome, becomes phosphorylated in neurons activated by a wide range of stimuli. We show that these phosphorylated ribosomes can be captured from mouse brain homogenates, thereby enriching directly for the mRNAs expressed in discrete subpopulations of activated cells. We use this approach to identify neurons in the hypothalamus regulated by changes in salt balance or food availability. We show that galanin neurons are activated by fasting and that prodynorphin neurons restrain food intake during scheduled feeding. These studies identify elements of the neural circuit that controls food intake and illustrate how the activity-dependent capture of cell-type-specific transcripts can elucidate the functional organization of a complex tissue.

Summary Statement Commensal bacteria are believed to play important roles in human health. The mechanisms by which they affect mammalian physiology are poorly understood; however, bacterial metabolites are likely to be key components of host interactions. Here, we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands although future studies are needed to define their potential physiologic role in humans. This work suggests that chemical mimicry of eukaryotic signaling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a new small molecule therapeutic modality (microbiome-biosynthetic-gene-therapy).

Background: There has been a dramatic shift in use of bariatric procedures, but little is known about their long-term comparative effectiveness. Objective: To compare weight loss and safety among bariatric procedures. Design: Retrospective observational cohort study, January 2005 to September 2015. (ClinicalTrials.gov: ) Setting: 41 health systems in the National Patient-Centered Clinical Research Network. Participants: 65 093 patients aged 20 to 79 years with body mass index (BMI) of 35 kg/m2 or greater who had bariatric procedures. Intervention: 32 208 Roux-en-Y gastric bypass (RYGB), 29 693 sleeve gastrectomy (SG), and 3192 adjustable gastric banding (AGB) procedures. Measurements: Estimated percent total weight loss (TWL) at 1, 3, and 5 years; 30-day rates of major adverse events. Results: Total numbers of eligible patients with weight measures at 1, 3, and 5 years were 44 978 (84%), 20 783 (68%), and 7159 (69%), respectively. Thirty-day rates of major adverse events were 5.0% for RYGB, 2.6% for SG, and 2.9% for AGB. One-year mean TWLs were 31.2% (95% CI, 31.1% to 31.3%) for RYGB, 25.2% (CI, 25.1% to 25.4%) for SG, and 13.7% (CI, 13.3% to 14.0%) for AGB. At 1 year, RYGB patients lost 5.9 (CI, 5.8 to 6.1) percentage points more weight than SG patients and 17.7 (CI, 17.3 to 18.1) percentage points more than AGB patients, and SG patients lost 12.0 (CI, 11.6 to 12.5) percentage points more than AGB patients. Five-year mean TWLs were 25.5% (CI,25.1% to 25.9%) for RYGB, 18.8% (CI, 18.0% to 19.6%) for SG, and 11.7% (CI, 10.2% to 13.1%) for AGB. Patients with diabetes, those with BMI less than 50 kg/m2, those aged 65 years or older, African American patients, and Hispanic patients lost less weight than patients without those characteristics. Limitation: Potential unobserved confounding due to nonrandomized design; electronic health record databases had missing outcome data. Conclusion: Adults lost more weight with RYGB than with SG or AGB at 1, 3, and 5 years; however, RYGB had the highest 30-day rate of major adverse events. Small subgroup differences in weight loss outcomes were observed. Primary Funding Source: Patient-Centered Outcomes Research Institute.

BackgroundBesides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF) is also involved in energy homeostasis and cardiovascular regulation. Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile.Methodology/Principal FindingsTo determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age ∼70), in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3), and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin.Conclusion/SignificancePlasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain) remains to be determined.