A5063697900- Adipose Tissue and Metabolism
- Diet and metabolism studies
- CRISPR and Genetic Engineering
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Diet, Metabolism, and Disease
- Sirtuins and Resveratrol in Medicine
- Genomics, phytochemicals, and oxidative stress
- Lipid metabolism and biosynthesis
- Gut microbiota and health
- Dietary Effects on Health
- Autophagy in Disease and Therapy
- Genetics, Aging, and Longevity in Model Organisms
- Tuberous Sclerosis Complex Research
- Biochemical effects in animals
- Genetic and Kidney Cyst Diseases
- Muscle Physiology and Disorders
- Mast cells and histamine
- Muscle metabolism and nutrition
Harvard University
2021-2022
National Institute on Aging
2020-2022
Boston VA Research Institute
2021
National Institutes of Health
2020
Upon nutrient stimulation, pre-adipocytes undergo differentiation to transform into mature adipocytes capable of storing nutrients as fat. We profiled cellular metabolite consumption identify early metabolic drivers adipocyte differentiation. find that raises the uptake and numerous amino acids. In particular, branched-chain acid (BCAA) catabolism precedes promotes peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator adipogenesis. adipogenesis, mitochondrial sirtuin...
Abstract Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes energy metabolism regulation. Here, inducible in mice transgenesis the target, NQO1, conferred protection from diet-induced defects through preservation glucose homeostasis, sensitivity, lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated association inhibition translational machinery skeletal muscle NQO1...
The mechanistic target of rapamycin complex 1 (mTORC1) is dynamically regulated by fasting and feeding cycles in the liver to promote protein lipid synthesis while suppressing autophagy. However, beyond these functions, metabolic response insulin signaling orchestrated mTORC1 remains poorly defined. Here, we determine whether ATF4, a stress responsive transcription factor recently found be independently proliferating cells, hepatic alter hepatocyte metabolism. ATF4 levels expression...
The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), as a sensor growth signals that subsequently controls cell growth, has been predominantly studied in actively proliferating cells. Primary cilia are sensory organelles present on most quiescent cells, where they play essential roles receiving environmental and developmental signals. Given ciliated cells non-proliferative, we investigated whether mTORC1 signaling influences the primary cilia. Here, show promotes elongation,...
There is increasing interest in utilizing short-term dietary interventions the contexts of cancer, surgical stress and metabolic disease. These diets may be more feasible than extended designed to complement existing therapies. In particular, high-fat, low-carbohydrate ketogenic diet (KD), traditionally used treat epilepsy, has gained popularity as a potential strategy for weight loss improved health. mice, long-term KD improves insulin sensitivity extend lifespan healthspan. Dietary protein...
Abstract Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at systemic and tissue levels is not fully understood. Here, adult old C57BL/6 male mice were assigned one three groups: sedentary, daily high-intensity intermittent (HIIT), or moderate intensity continuous (MICT) for 4 weeks, compatible older group’s capacity. Improvements in body composition, fasting blood glucose, strength mostly observed MICT group, while effects HIIT...
Dietary protein restriction (PR) has rapid effects on metabolism including improved glucose and lipid homeostasis, via multiple mechanisms. Here, we investigate responses of fecal microbiome, hepatic transcriptome, metabolome to six diets with from 18% 0% energy in mice. PR alters microbial composition, but metabolic are not transferable transplantation. Hepatic transcriptome significantly altered lower than 10% protein. Changes upon correlate calorie a larger magnitude specific changes...
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates diverse intracellular and extracellular growth signals to regulate cell tissue growth. How the molecular mechanisms regulating mTORC1 signaling established through biochemical biological studies function under physiological states in specific mammalian tissues are unknown. Here, we characterize a genetic mouse model lacking 5 phosphorylation sites on tuberous sclerosis 2 (TSC2) protein which factor-stimulated kinase AKT can...
Abstract Objective The mechanistic target of rapamycin complex 1 (mTORC1) is dynamically regulated by fasting and feeding cycles in the liver to promote protein lipid synthesis while suppressing autophagy. However, beyond these functions, metabolic response insulin signaling orchestrated mTORC1 remains poorly defined. Here, we determine whether ATF4, a stress responsive transcription factor recently found be independently proliferating cells, hepatic alter hepatocyte metabolism. Methods ATF4...
The number of adults aged 65 and older in the United States globally is expected to nearly double size by 2050. It will be necessary devise strategies spanning science, healthcare, regulatory sectors support growing adapt changes population aging. Given greater disease risk individuals, this shift also presents new opportunities for research development both preventive therapeutic interventions that target a wide range chronic conditions. Many previous articles have focused on advantages...
Abstract There is increasing interest in utilizing short-term dietary interventions the contexts of cancer, surgical stress and metabolic disease. These diets may be more feasible than extended designed to complement existing therapies. In particular, high-fat, low-carbohydrate ketogenic diet (KD), traditionally used treat epilepsy, has gained popularity as a potential strategy for weight loss improved health. mice, long-term KD improves insulin sensitivity extends lifespan healthspan....