A5046569779- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- Sirtuins and Resveratrol in Medicine
- Pediatric Hepatobiliary Diseases and Treatments
- Metabolism, Diabetes, and Cancer
- Metabolomics and Mass Spectrometry Studies
- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Calcium signaling and nucleotide metabolism
- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- Regulation of Appetite and Obesity
- Cannabis and Cannabinoid Research
- HIV/AIDS drug development and treatment
- Physiological and biochemical adaptations
- Stress Responses and Cortisol
- Cancer, Hypoxia, and Metabolism
- TGF-β signaling in diseases
- PARP inhibition in cancer therapy
- Sleep and Wakefulness Research
- Meta-analysis and systematic reviews
- Cancer Cells and Metastasis
- Plant Molecular Biology Research
- Autophagy in Disease and Therapy
Beth Israel Deaconess Medical Center
2019-2023
Harvard University
2020-2023
Hadassah Medical Center
2019-2020
ETH Zurich
2014-2018
University of Zurich
2018
Tata Institute of Fundamental Research
2010-2017
MicroRNA mir-9 is speculated to be involved in insulin secretion because of its ability regulate exocytosis. Sirt1 an NAD-dependent protein deacetylase and a critical factor the modulation cellular responses altered metabolic flux. It has also been shown recently control from pancreatic β-islets. However, little known about regulation levels β-cells, particularly during glucose-dependent secretion. In this article, we report that are actively regulated vivo β-islets Our data demonstrates...
Maintaining a healthy body weight requires an exquisite balance between energy intake and expenditure. To understand the genetic environmental factors that contribute to regulation of weight, important first step is establish normal range metabolic values primary sources contributing variability. Energy metabolism measured by powerful sensitive indirect calorimetry devices. Analysis nearly 10,000 wild-type mice from two large-scale experiments revealed largest variation in expenditure due...
Bile acids play crucial roles in host physiology by acting both as detergents that aid digestion and signaling molecules bind to receptors. Gut bacterial bile salt hydrolase (BSH) enzymes perform the gateway reaction leading conversion of host-produced primary into bacterially modified secondary acids. Small molecule probes target BSHs will help elucidate causal these metabolites physiology. We previously reported development a covalent BSH inhibitor with low gut permeability. Here, we build...
The small intestine is the main organ involved in digestion and absorption of nutrients. It an ideal position to sense availability energy lumen addition its absorptive function. Consumption a high-fat diet (HFD) influences metabolic characteristics intestine. Therefore, better understand features their changes response dietary fat, we characterized metabolism duodenal, jejunal, hepatic cell lines assessed enterocytes liver after short-term (3 days) or medium-term (14 HFD feeding mice....
The endogenous lipid messenger oleoylethanolamide (OEA) inhibits eating and modulates fat metabolism supposedly through the activation of peroxisome proliferator-activated receptor-α (PPARα) vagal sensory fibers. We tested in adult male rats whether OEA stimulates fatty acid oxidation (FAO) ketogenesis it increases plasma levels satiating gut peptides glucagon-like peptide-1 (GLP-1) peptide YY (PYY). also explored still after subdiaphragmatic deafferentation (SDA). found that...
This study was performed to determine the effect of fasting on reproducibility glucose tolerance test. Due individual variation in animal feeding behaviors, animals prior metabolic and behavioral experiments is widely held reduce inter-subject parameters preclinical rodent models. Reducing variability especially important for studies where initial metabolite levels can influence magnitude experimental interventions, but also imposes stress that may distort variables interest. One such...
The intestinal epithelium plays an essential role in nutrient absorption, hormone release, and barrier function. Maintenance of the is driven by continuous cell renewal stem cells located crypts. amount type diet influence this process result changes size cellular make-up tissue. mechanism underlying nutrient-driven proliferation not known, but may involve a shift intracellular metabolism that allows for more nutrients to be used manufacture new cells. We hypothesized availability drives...
Intestinal metabolism might play a greater role in regulating whole body than previously believed. We aimed to enhance enterocyte mice and investigate if it plays diet-induced obesity (DIO) its comorbidities.
The conserved NAD+-dependent deacylase SIRT1 plays pivotal, sometimes contrasting, roles in diverse physiological and pathophysiological conditions. In this study, we uncover a tissue-restricted isoform of (SIRT1-ΔE2) that lacks exon 2 (E2). Candidate-based screening substrates demonstrated the domain encoded by key role specifying protein-protein interactions. E2 was both necessary sufficient for PGC1α binding, enhanced interaction with p53, thus downstream functions. Since SIRT1-FL...
Abstract Studies indicate that modulating enterocyte metabolism might affect whole body glucose homeostasis and the development of diet-induced obesity (DIO). We tested whether enhancing fatty acid oxidation (FAO) could protect mice from DIO impaired glycemic control. To this end, we used expressing a mutant form carnitine palmitoyltransferase-1a (CPT1mt), insensitive to inhibition by malonyl-CoA, in their enterocytes (iCPT1mt) fed them low-fat control diet (CD) or high-fat (HFD)...
Thylakoids reduce body weight gain and fat accumulation in rodents. This study investigated whether an enhanced oxidation of dietary fat-derived fatty acids the intestine contributes to thylakoid effects. Male Sprague-Dawley rats were fed a high-fat diet with (n = 8) or without thylakoids for 2 wk. Body weight, food intake, measured, intestinal mucosa was collected analyzed. Quantitative real-time PCR used measure gene expression levels key enzymes involved acid transport, oxidation,...
Hepatic fatty acid oxidation (FAO) has long been implicated in the control of eating. Nevertheless, direct evidence for a causal relationship between changes hepatic FAO and food intake is still missing. Here we tested whether increasing via adenovirus-mediated expression mutated form key regulatory enzyme mitochondrial carnitine palmitoyltransferase 1A (CPT1mt), which active but insensitive to inhibition by malonyl-CoA, affects eating metabolism mice. CPT1mt increased hepatocellular CPT1...
Abstract Maintaining a healthy body weight requires an exquisite balance between energy intake and expenditure. In humans in laboratory mice these factors are experimentally measured by powerful sensitive indirect calorimetry devices. To understand the genetic environmental that contribute to regulation of weight, important first step is establish normal range metabolic values primary sources contributing variability results. Here we examine results from two experimental mouse projects,...
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Abstract Bile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. acids regulate key metabolic immune processes binding host receptors. There is an unmet need for a potent tool inhibit BSHs across all in order study effects of on physiology. Here, we report development covalent pan-inhibitor bacterial BSH. From rationally designed candidate library, identified lead compound bearing...
ABSTRACT Growth differentiation factor 3 (GDF3) is a relatively understudied member of the TGFβ superfamily that highly expressed during development. However, function GDF3 in adult biology contentious. We use vivo approaches to show loss-of-function adipose tissue obese mice causes reduced body weight and improved whole-body insulin sensitivity. These effects are accompanied by altered regulation genes targeted . Using vitro approaches, we can influence both arms superfamily: simultaneously...
Abstract Bile acids play crucial roles in host physiology by acting as both detergents that aid digestion and signaling molecules bind to receptors. Gut bacterial bile salt hydrolase (BSH) enzymes perform the gateway reaction leading conversion of host-produced primary into bacterially modified secondary acids. Small molecule probes target BSHs will help elucidate causal these metabolites physiology. We previously reported development a covalent BSH inhibitor with low gut permeability. Here,...
Abstract Overnutrition and obesity promote adipose tissue dysfunction, often leading to systemic insulin resistance. The thiazolidinediones (TZDs) are a potent class of insulin-sensitizing drugs ligands PPARγ that improve sensitivity, but their use is limited due significant side effects. Recently, we demonstrated mechanism by which TZDs sensitivity distinct from receptor agonism adipogenesis: reversal obesity-linked phosphorylation at Serine 273. However, the role this modification has not...