A5065622211- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Biochemical Analysis and Sensing Techniques
- Telecommunications and Broadcasting Technologies
- Adipokines, Inflammation, and Metabolic Diseases
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- Sleep and Wakefulness Research
- Genetic Associations and Epidemiology
- MicroRNA in disease regulation
- Neuroendocrine regulation and behavior
- Photoreceptor and optogenetics research
- RNA modifications and cancer
- Nutrition, Genetics, and Disease
- Receptor Mechanisms and Signaling
- Advanced MIMO Systems Optimization
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- Cancer-related molecular mechanisms research
- Genetic Mapping and Diversity in Plants and Animals
- Ion Channels and Receptors
- Neuropeptides and Animal Physiology
- Animal Genetics and Reproduction
- Neurobiology and Insect Physiology Research
- Neuroscience and Neuropharmacology Research
Rockefeller University
2016-2025
Howard Hughes Medical Institute
2016-2025
Laboratory of Molecular Genetics
2004-2024
USC Norris Comprehensive Cancer Center
2009-2023
New York Proton Center
2022-2023
University of Florida
2022
Vanderbilt University Medical Center
2013-2014
University of California, Los Angeles
2012
University of Southern California
2006-2011
Imaging Center
2008
The gene product of the ob locus is important in regulation body weight. was shown to be present as a 16-kilodalton protein mouse and human plasma but undetectable from C57BL/6J / mice. Plasma levels this were increased diabetic ( db ) mice, mutant thought resistant effects . Daily intraperitoneal injections either or recombinant OB reduced weight mice by 30 percent after 2 weeks treatment with no apparent toxicity had effect on food intake energy expenditure Injections wild-type twice daily...
We report the construction of a genetic linkage map mouse, consisting entirely markers that can be rapidly typed by polymerase chain reaction and show high degree polymorphism among inbred laboratory strains. Specifically, contains 317 simple sequence length polymorphisms at an average spacing 4.3 cM is detectably linked to approximately 99% mouse genome. In typical crosses between strains, about 50% are polymorphic, making it straightforward follow inheritance in almost any cross.
Stearoyl–CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), which are components membrane phospholipids, triglycerides, wax esters, cholesterol esters. Several SCD isoforms ( SCD1 - 3 ) exist in mouse. Here we show that mice with targeted disruption isoform have reduced body adiposity, increased insulin sensitivity, resistant to diet-induced weight gain. The protection from obesity...
Recent data have identified leptin as an afferent signal in a negative-feedback loop regulating the mass of adipose tissue. High levels are observed obese humans and rodents, suggesting that, some cases, obesity is result insensitivity. This hypothesis was tested by comparing response to peripherally centrally administered among lean three strains mice: diet-induced AKR/J, New Zealand Obese (NZO), A y . Subcutaneous infusion mice resulted dose-dependent loss body weight at physiologic plasma...
The fat-derived hormone leptin regulates energy balance in part by modulating the activity of neuropeptide Y and proopiomelanocortin neurons hypothalamic arcuate nucleus. To study intrinsic these their responses to leptin, we generated mice that express distinct green fluorescent proteins two neuronal types. Leptin-deficient (ob/ob) differed from wild-type numbers excitatory inhibitory synapses postsynaptic currents onto neurons. When was delivered systemically ob/ob mice, synaptic density...
Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. To examine the mechanism underlying leptin's actions, we used transcription profiling to identify leptin-regulated genes in ob/ob liver. was found specifically repress RNA levels and enzymatic activity of hepatic stearoyl–CoA desaturase-1 (SCD-1), which catalyzes biosynthesis monounsaturated fatty acids. Mice lacking SCD-1 were lean hypermetabolic. mice with mutations significantly less obese than...
Leptin’s effects are mediated by interactions with a receptor that is alternatively spliced, resulting in at least five different murine forms: Ob-Ra, Ob-Rb, Ob-Rc, Ob-Rd, and Ob-Re. A mutation one splice form, results obesity mice. Northern blots, RNase protection assays, PCR indicate Ob-Rb expressed relatively high level hypothalamus low several other tissues. Ob-Ra ubiquitously, whereas -Rd, -Re RNAs only detectable using PCR. In hypothalamus, present the arcuate, ventromedial,...
Osmotic homeostasis is one of the most aggressively defended physiological parameters in vertebrates. However, molecular mechanisms underlying osmotic regulation are poorly understood. The transient receptor potential channel, vanilloid subfamily (TRPV4), an osmotically activated ion channel that expressed circumventricular organs mammalian CNS, which important site sensing. We have generated trpv4 -null mice and observed abnormalities their regulation. -/- drank less water became more...
Animals with mutations in the leptin receptor (ObR) exhibit an obese phenotype that is indistinguishable from of deficient ob/ob mice. ObR expressed many tissues, including brain, and relative importance leptin’s effects on central versus peripheral sites has not been resolved. To address this, we generated mice neuron-specific (ObRSynIKO) hepatocyte-specific (ObRAlbKO) disruption ObR. Among ObRSynIKO mice, extent obesity was negatively correlated level hypothalamus those animals lowest...
Leptin is a hormone that regulates body weight by decreasing food intake and increasing energy expenditure. ob/ob mice carry leptin mutations are obese hyperphagic. administration to lean activates novel metabolic program depletes adipose tissue. Although this response physiologically distinct from evident after restriction, the molecular nature of these differences as yet unknown. Expression monitoring 6500 genes using oligonucleotide microarrays in wild-type, , transgenic expressing low...
We present GERMLINE, a robust algorithm for identifying segmental sharing indicative of recent common ancestry between pairs individuals. Unlike methods with comparable objectives, GERMLINE scales linearly the number samples, enabling analysis whole-genome data in large cohorts. Our approach is based on dictionary haplotypes that used to efficiently discover short exact matches then expand these using dynamic programming identify long, nearly identical relatedness. use comprehensively survey...