A5058266159- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolomics and Mass Spectrometry Studies
- Regulation of Appetite and Obesity
- Immune Cell Function and Interaction
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Eicosanoids and Hypertension Pharmacology
- Peroxisome Proliferator-Activated Receptors
- Neurological Disease Mechanisms and Treatments
- Complement system in diseases
- Total Knee Arthroplasty Outcomes
- Exercise and Physiological Responses
- Muscle metabolism and nutrition
- Cardiovascular Function and Risk Factors
- Immune Response and Inflammation
- Osteoarthritis Treatment and Mechanisms
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Orthopaedic implants and arthroplasty
- Sleep and Wakefulness Research
- Fatty Acid Research and Health
- Sirtuins and Resveratrol in Medicine
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Massachusetts General Hospital
2017-2024
Harvard University
2014-2024
Center for Pain and the Brain
2022
Dana-Farber Cancer Institute
2012-2020
Harvard Stem Cell Institute
2019-2020
Broad Institute
2019
Beth Israel Deaconess Medical Center
2011-2015
Diabetes Australia
2012
Hadassah Medical Center
2012
Cornell University
2011
Physical activity provides clinical benefit in Parkinson’s disease (PD). Irisin is an exercise-induced polypeptide secreted by skeletal muscle that crosses the blood–brain barrier and mediates certain effects of exercise. Here, we show irisin prevents pathologic α-synuclein (α-syn)-induced neurodegeneration α-syn preformed fibril (PFF) mouse model sporadic PD. Intravenous delivery via viral vectors following stereotaxic intrastriatal injection PFF cause a reduction formation prevented loss...
A pathological hallmark of Alzheimer's disease (AD) is the deposition amyloid-β (Aβ) protein in brain. Physical exercise has been shown to reduce Aβ burden various AD mouse models, but underlying mechanisms have not elucidated. Irisin, an exercise-induced hormone, secreted form fibronectin type-III-domain-containing 5 (FNDC5). Here, using a three-dimensional (3D) cell culture model AD, we show that irisin significantly reduces pathology by increasing astrocytic release Aβ-degrading enzyme...
Obesity is associated with an elevated risk for several types of cancer and thus a major health hazard. However, the mechanism between overweight susceptibility still elusive. Leptin, mainly produced by adipocytes links food intake energy expenditure. In addition, recent studies have shown immunomodulatory impact leptin on NK cells. The purpose present study was to investigate whether stimulation cells from obese humans leads altered functions as compared lean subjects. On basis body mass...
Exercise can improve cognitive function and the outcome of neurodegenerative diseases, like Alzheimer's disease. This effect has been linked to increased expression brain-derived neurotrophic factor (BDNF). However, underlying molecular mechanisms driving elevation this neurotrophin remain unknown. Recently, we have reported a PGC-1α-FNDC5/irisin pathway, which is activated by exercise in hippocampus mice induces neuroprotective gene program, including Bdnf. review will focus on FNDC5 its...
Significance The work reported in this paper describes a previously unknown signaling pathway skeletal muscle acting through G protein-coupled receptor 56-Galpha12/13. This discovery elucidates mechanism of anabolism and gives another target investigation for therapies against the loss mass seen with aging various wasting diseases.
Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. vitro, (2-10 ng/mL) increased osteoclast differentiation C57BL/6J mouse bone marrow progenitors; however, increase was blocked neutralizing antibody to integrin αVβ5. Irisin also resorption several substrates situ. RNAseq revealed differential gene expression induced...
Epidemiological studies have indicated that obesity is associated with a higher risk for certain cancers caused by elevated levels of adipocyte-derived hormones. Leptin, one such hormone produced adipocytes, major regulator metabolism and has also been shown to modulate immunity. However, its role in regulating human natural killer (NK) cell functions largely unknown. Here, we show the leptin receptor (Ob-R) expressed on 5% NK cells isolated from blood donors, as measured flow cytometry,...
Diabetes risk increases significantly with age and correlates lower oxidative capacity in muscle. Decreased expression of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) target gene pathways involved mitochondrial phosphorylation are associated muscle insulin resistance, but a causative role has not been established. We sought to determine whether decline Pgc-1α occurs during aging potentiates the development age-associated resistance. Muscle-specific knockout (MKO) mice...
The adipocyte-derived hormone leptin is a critical regulator of many physiological functions, ranging from satiety to immunity. Surprisingly, very little known about the transcriptional pathways that regulate adipocyte-specific expression leptin. Here, we report studies in which pursued strategy integrating BAC transgenic reporter mice, assays, and chromatin state mapping locate an cis-element upstream (LEP) gene human fat cells. Quantitative proteomics with affinity enrichment protein-DNA...
Objective Natural killer (NK) cells are the first defense against malignant cells, and their functions severely impaired in individuals with obesity. However, it is not known whether can be re-activated after weight loss. The alterations of NK cell fat mass reduction were investigated. Methods Thirty-two healthy adults obesity divided into control experimental groups. Participants group performed a 3-month program exercise training nutrition. Anthropometric, physiological, metabolic...
The double burden of under‐ and overnutrition profoundly affects human health globally. According to the World Health Organization, obesity diabetes rates have almost doubled worldwide since 1980, and, in 2011, more than 40 million children under 5 years age were overweight. Ecologic factors, parental genetics fitness, intrauterine environment significantly influence likelihood offspring developing dysmetabolic diathesis obesity. This report examines effects these including preconception,...
Abstract The PI3K/Akt signaling pathway has been recently suggested to have controversial functions in models of acute and chronic inflammation. Our group others reported previously that the complement split product C5a alters neutrophil innate immunity cell during onset sepsis is involved PI3K activation. We report this study vivo inhibition resulted increased mortality septic mice accompanied by strongly elevated serum levels TNF-α, IL-6, MCP-1, IL-10 as well decreased oxidative burst...
Breast cancer continues to be a major cause of deaths in women. Estrogen, which is also produced by the adipose tissue, held responsible for elevated risk breast obese However, tissue secrets hormones and adipokines such as leptin IGF-I these substances could contribute an increased In this study, impact obesity on cell proliferation was investigated. The carcinogen 7, 12, dimethylbenz[a]anthracene (DMBA) administered normal weight diet-induced female Sprague-Dawley rats. Cell evaluated...
The adipocyte-derived hormone leptin is a critical regulator of many physiological functions, ranging from satiety to immunity. Surprisingly, very little known about the transcriptional pathways that regulate adipocyte-specific expression leptin. In recent published study, we pursued strategy integrating BAC transgenic reporter mice, in vitro assays, and chromatin state mapping locate an cis-element upstream LEP gene human fat cells. Quantitative proteomics (stable isotope labeling by amino...
Background Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations both adipogenesis the production adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are host's primary defense against virus-infected tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions two distinct human NK cell subsets. Methods Isolated peripheral blood mononuclear (PBMCs) were cultured with...