A5003782625- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Neuropeptides and Animal Physiology
- Adipokines, Inflammation, and Metabolic Diseases
- Peroxisome Proliferator-Activated Receptors
- Pancreatic function and diabetes
- Hormonal Regulation and Hypertension
- Stress Responses and Cortisol
- Diet and metabolism studies
- Lipid metabolism and biosynthesis
- Hypothalamic control of reproductive hormones
- Diet, Metabolism, and Disease
- Receptor Mechanisms and Signaling
- Diabetes and associated disorders
- Biochemical Analysis and Sensing Techniques
- Neuroendocrine regulation and behavior
- Molecular Biology Techniques and Applications
- RNA Research and Splicing
- Renal function and acid-base balance
- Neuroscience of respiration and sleep
- Respiratory Support and Mechanisms
- Hemodynamic Monitoring and Therapy
- Cardiovascular Disease and Adiposity
- Apelin-related biomedical research
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
University of Northern British Columbia
2011-2023
University of Minnesota
2011-2018
Positive Living North
2012
University of British Columbia
2005-2011
Michigan Technological University
2010
Addenbrooke's Hospital
2004-2008
University of Cambridge
2004-2008
University of Victoria
2001-2007
Rockefeller University
2004
Institute of Cancer Research
2004
Inherited defects in signaling pathways downstream of the insulin receptor have long been suggested to contribute human type 2 diabetes mellitus. Here we describe a mutation gene encoding protein kinase AKT2/PKBβ family that shows autosomal dominant inheritance severe resistance and Expression mutant cultured cells disrupted metabolic end points inhibited function coexpressed, wild-type AKT. These findings demonstrate central importance AKT sensitivity humans.
Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation PPARg2 in ob/ob background, PPARg2−/− Lepob/Lepob (POKO mouse), resulted decreased fat mass, severe insulin resistance, β-cell failure, and dyslipidaemia. Our results indicate that plays an important role, mediating adipose tissue expansion response to positive energy balance. Lipidomic analyses suggest antilipotoxic role when induced ectopically liver muscle by facilitating...
Drug-dependent neural plasticity related to drug addiction and schizophrenia can be modeled in animals as behavioral sensitization, which is induced by repeated noncontingent or self-administration of many drugs abuse. Molecular mechanisms that are critical for sensitization have yet specified. Long-term depression (LTD) α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor (AMPAR)–mediated synaptic transmission the brain has been proposed a cellular substrate learning memory. The...
Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder featuring near complete absence of adipose tissue. Remarkably, although the causative gene, BSCL2, has been known for several years, its molecular function and role in tissue development have not elucidated. Therefore, we examined whether BSCL2 involved regulation adipocyte differentiation mechanism whereby pathogenic mutations cause lipodystrophy.
Abstract Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hormone belonging to the glucagon superfamily of hormones. These hormones are known play important roles in metabolism and growth. PACAP neuropeptide that causes accumulation cAMP number tissues affects secretion other hormones, vasodilation, neural immune functions, as well cell cycle. To determine whether essential for survival evaluate its function(s), we have generated mice lacking gene via homologous recombination....
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved hormone. Targeted disruption of the PACAP gene has revealed role for this peptide in lipid metabolism, carbohydrate and sympathetic response to insulin stress. We report here that null mice are temperature sensitive. When raised at 21 C, only 11% survived past first 2 wk after birth, but when 24 most (76%) survived. The question mechanism by which absence affects thermoregulation. Brown adipose tissue major site...
The adipocyte hormone leptin acts centrally and peripherally to regulate body weight glucose homeostasis. pancreatic β-cell has been shown be a key peripheral target of leptin, with suppressing insulin synthesis secretion from β-cells both in vitro vivo. Mice disrupted signaling (leprflox/flox RIPcre tg+ mice) display hyperinsulinemia, resistance, intolerance, obesity, reduced fasting blood glucose. We hypothesized that hyperinsulinemia precedes the development resistance increased adiposity...
The liver plays a critical role in integrating and controlling glucose metabolism. Thus, it is important that the receive react to signals from other tissues regarding nutrient status of body. Leptin, which produced secreted adipose tissue, hormone relays information depots parts Leptin has profound influence on metabolism, so we sought determine if leptin may exert this effect part through liver.To explore possibility, created mice have disrupted hepatic signaling using Cre-lox approach...
Evidence from recent epidemiological studies has emerged implicating exposure to environmental toxicants as a novel risk factor for the development of type 2 diabetes (T2D) and metabolic syndrome in general population. Humans other organisms high trophic levels food chain consume persistent organic pollutants (POP) through their diet. Few experimental demonstrating cause effect are available evidence direct association between accumulation POP T2D is preliminary; however, possibility exists...
Peroxisome proliferator–activated receptor (PPAR)γ is a key transcription factor facilitating fat deposition in adipose tissue through its proadipogenic and lipogenic actions. Human patients with dominant-negative mutations PPARγ display lipodystrophy extreme insulin resistance. For this reason it was completely unexpected that mice harboring an equivalent mutation (P465L) developed normal amounts of were sensitive. This finding raised important doubts about the interspecies translatability...
Previous studies have demonstrated that pituitary adenylate cyclase-activating polypeptide (PACAP) exerts trophic effects during neurodevelopment. In particular, the occurrence of PACAP and its receptors in cerebellum pre- postnatal periods suggests it could play a crucial role ontogenesis this structure. To test hypothesis, we compared histogenesis cerebellar cortex wild-type PACAP-knockout (PACAP-/-) mice at days (P)4 7. Morphometric analysis PACAP-/- revealed significant reduction...
Mice with a dominant-negative peroxisome proliferator-activated receptor gamma (PPARgamma) mutation (P465L) unexpectedly had normal amounts of adipose tissue. Here, we investigate the tissue PPARgamma P465L mouse in detail. Microscopic analysis interscapular mice revealed brown adipocytes larger unilocular lipid droplets, indicative reduced thermogenic capacity. Under conditions cold exposure, was less active, fact reflected decreased uncoupling protein 1 levels. Analysis white confirmed...
Disruption of the pituitary adenylate cyclase-activating polypeptide (PACAP) gene in mice has demonstrated a role for this highly conserved neuropeptide regulation metabolism and temperature control. Localization PACAP neurons within hypothalamic nuclei that regulate appetite suggest may affect feeding thus energy balance. We used PACAP-null to address question, examining both food intake expenditure. were leaner than wild-type littermates due decreased adiposity displayed increased insulin...
Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triacylglycerol (TG) synthesis. Despite existence an alternative (DGAT1), mice lacking DGAT2 have a severe deficiency TG in adipose tissue, indicating nonredundant role for this enzyme adipocyte We studied regulation expression during adipogenesis. In both isolated murine preadipocytes and 3T3-L1 cells temporal pattern closely mimicked that genes whose is regulated by CAAT/enhancer-binding protein beta (C/EBPbeta)....
Leptin, an adipocyte-derived hormone, plays essential role in the maintenance of normal body weight and energy expenditure, as well glucose homeostasis. Indeed, leptin-deficient ob/ob mice are obese with profound hyperinsulinemia, insulin resistance, often hyperglycemia. Interestingly, low doses exogenous leptin can reverse hyperinsulinemia hyperglycemia these animals without altering weight. The may result directly from absence signaling pancreatic β-cells and, turn, contribute to both...
Humans with inactivating mutations in peroxisomal proliferators activated receptor gamma (PPARgamma) typically develop a complex metabolic syndrome characterized by insulin resistance, diabetes, lipodystrophy, hypertension, and dyslipidaemia which is likely to increase their cardiovascular risk. Despite evidence that the activation of PPARgamma may prevent cardiac fibrosis hypertrophy, recent has suggested pharmacological causes increased mortality. In this study, we investigated effects...
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hormone belonging to the glucagon superfamily of hormones. These hormones are known play important roles in metabolism and growth. PACAP neuropeptide that causes accumulation cAMP number tissues affects secretion other hormones, vasodilation, neural immune functions, as well cell cycle. To determine whether essential for survival evaluate its function(s), we have generated mice lacking gene via homologous recombination. We found...
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widely distributed neuropeptide that acts as neurotransmitter, neuromodulator, neurotropic factor, neuroprotectant, secretagogue, and neurohormone. Owing to its pleiotropic biological actions, knockout of Pacap ( Adcyap1 ) has been shown induce several abnormalities in mice such impaired thermoregulation. However, the underlying physiological molecular mechanisms remain unclear. A previous report cold-exposed null cannot supply...
Obesity arises from disrupted energy balance and is caused by chronically higher intake compared to expenditure via basal metabolic rate, exercise, thermogenesis. The brown adipose tissue (BAT), the primary thermogenic organ, has received considerable attention as a potential therapeutic target due its ability burn lipids in production of heat. Pituitary adenylate cyclase-activating polypeptide (PACAP) been identified key regulator physiological stress response both centrally peripherally....
In vivo genetic manipulation is used to study the impact of gene deletion or re-expression on β-cell function and organism physiology. Cre-LoxP a system wherein LoxP sites flanking are recognized by Cre recombinase. transgenic mice most prevalent technology deliver but many models have caveats off-target recombination, impaired function, high cost animal production. Inducible estrogen receptor conjugated face leaky recombination confounding effects tamoxifen. As an alternative, we...