A5013371851- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Diet, Metabolism, and Disease
- Regulation of Appetite and Obesity
- Liver physiology and pathology
- FOXO transcription factor regulation
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and disorders
- Endoplasmic Reticulum Stress and Disease
- Genetics and Neurodevelopmental Disorders
- Diabetes Management and Research
- Diabetes Treatment and Management
- Diet and metabolism studies
- Kruppel-like factors research
- Lipid metabolism and biosynthesis
- Cardiovascular Function and Risk Factors
- MicroRNA in disease regulation
- COVID-19 Clinical Research Studies
- PI3K/AKT/mTOR signaling in cancer
- Autophagy in Disease and Therapy
- Pancreatic and Hepatic Oncology Research
Columbia University
2015-2025
Columbia University Irving Medical Center
2015-2024
Center for Digestive and Liver Diseases
2024
Herbert Irving Comprehensive Cancer Center
2024
New York Proton Center
2019-2021
Manipal Hospital
2019
Albert Einstein College of Medicine
2003-2007
Yeshiva University
2004-2005
Merck & Co., Inc., Rahway, NJ, USA (United States)
2000
Massachusetts Institute of Technology
1997
Adiponectin is an adipocyte-specific secretory protein that circulates in serum as a hexamer of relatively low molecular weight (LMW) and larger multimeric structure high (HMW). Serum levels the correlate with systemic insulin sensitivity. The full-length affects hepatic gluconeogenesis through improved sensitivity, proteolytic fragment adiponectin stimulates β oxidation muscle. Here, we show ratio, not absolute amounts, between these two oligomeric forms (HMW to LMW) critical determining We...
Acrp30/adiponectin is an adipocyte-specific secretory protein that has recently been implicated as a mediator of systemic insulin sensitivity with liver and muscle target organs. Acrp30 found two forms in serum, lower molecular weight trimer-dimer high complex. Little know about the regulation significance these complexes serum events lead to generation bioactive ligand. Here, we show there profound sexual dimorphism levels complex distribution serum. Female mice display significantly higher...
The adipose tissue-derived hormone adiponectin improves insulin sensitivity and its circulating levels are decreased in obesity-induced resistance. Here, we report the generation of a mouse line with genomic disruption locus. We aimed to identify whether these mice develop resistance which primary target tissues affected this model. Using euglycemic/insulin clamp studies, demonstrate that display severe hepatic but not peripheral Furthermore, wanted test lack magnifies impairments glucose...
Adiponectin is a plasma protein expressed exclusively in adipose tissue. levels are linked to insulin sensitivity, but direct effect of chronically elevated adiponectin on improved sensitivity has not yet been demonstrated. We identified dominant mutation the collagenous domain that circulating values mice by 3-fold. Adiponectinemia raised lipid clearance and lipoprotein lipase activity, suppressed insulin-mediated endogenous glucose production. The induction during puberty sexual dimorphism...
Aberrant hepatocyte Notch activation is required for development of NASH-associated fibrosis, and inhibition ameliorates obesity-induced liver disease.
Abstract The rising prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) poses a significant global health challenge, affecting over 30% adults worldwide. MASLD is linked to increased mortality rates and substantial healthcare costs, primarily driven by its progression steatohepatitis (MASH), which can lead severe complications including cirrhosis hepatocellular carcinoma. Despite growing burden, effective pharmacotherapy for MASLD/MASH has been lacking until the...
Abstract Hepatic stellate cells (HSCs) have a central pathogenetic role in the development of liver fibrosis. However, their fibrosis-independent and homeostatic functions remain poorly understood 1–5 . Here we demonstrate that genetic depletion HSCs changes WNT activity zonation hepatocytes, leading to marked alterations regeneration, cytochrome P450 metabolism injury. We identify R-spondin 3 (RSPO3), an HSC-enriched modulator signalling, as responsible for these hepatocyte-regulatory...
Resistin was originally reported as an adipose tissue–specific hormone that provided a link between obesity and diabetes. protein level elevated in obese mice decreased by insulin-sensitizing thiazolidinediones. Immunoneutralization of resistin improved insulin sensitivity diet-induced mice, while the administration exogenous induced resistance. More recently, we have shown ablation gene fasting glucose through impairment gluconeogenesis, treatment these knockout increased hepatic...
The design of biomaterials containing specific ligands on the surface offers possibility creating materials that can interact with and potentially control mammalian cell behavior. Biodegradable further provide significant advantage polymer will disappear in vivo, obviating long-term negative tissue responses as well need for retrieval. In earlier studies we synthesized characterized arginine—glycine—aspartic acid (RGD) peptide-modified poly(lactic acid-co-lysine) (PLAL). this study, both...
Whereas thiazolidinediones (TZDs) are known to rapidly improve insulin action in animals, short durations of TZD therapy have never been studied humans. Among the many actions TZDs, increased circulating levels high molecular weight (HMW) multimer adiponectin may be an important insulin-sensitizing mechanism. We examined effects only 21 days 45 mg pioglitazone (P+) versus placebo (P−) nine subjects with type 2 diabetes (HbA1c, 10.9 ± 0.6%; BMI, 31.9 1.5 kg/m2). Total by approximately twofold...
OBJECTIVE—Adiponectin is an adipocyte-specific secretory protein found in circulation several different forms and present at significantly lower levels the plasma of diabetic patients compared with that insulin-sensitive individuals. We wanted to test whether insulin per se a contributing factor toward adiponectin concentrations and, if so, splanchnic bed contributes this phenomenon. RESEARCH DESIGN AND METHODS—We sampled femoral artery hepatic venous samples measured high–molecular weight...
Mechanistic target of rapamycin complex 1 (MTORC1) is a critical negative regulator general autophagy. We hypothesized that MTORC1 may specifically regulate autophagic clearance damaged mitochondria. To test this, we used cells lacking tuberous sclerosis 2 (TSC2-/- cells), which show constitutive activation. TSC2-/- MTORC1-dependent impaired flux after chemical uncoupling mitochondria, increased mitochondrial-protein aging, and accumulation p62/SQSTM1-positive Mitochondrial autophagy...
Obesity and high saturated fat intake increase the risk of heart failure arrhythmias. The molecular mechanisms are poorly understood. We hypothesized that physiologic levels could mitochondrial reactive oxygen species (ROS) in cardiomyocytes, leading to abnormalities calcium homeostasis function. investigated effect on function isolated ventricular myocytes. fatty acid palmitate causes a decrease respiration cardiomyocytes. Palmitate, but not monounsaturated oleate, an both total cellular...