A5106124932- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Muscle metabolism and nutrition
- Liver Disease Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Peroxisome Proliferator-Activated Receptors
- Muscle Physiology and Disorders
- Nuclear Receptors and Signaling
- Pancreatic function and diabetes
- Exercise and Physiological Responses
- GDF15 and Related Biomarkers
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Coenzyme Q10 studies and effects
- Cancer, Lipids, and Metabolism
- Cardiovascular and exercise physiology
- Autophagy in Disease and Therapy
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Pharmacological Effects and Assays
- Diet, Metabolism, and Disease
- Sirtuins and Resveratrol in Medicine
- Ion channel regulation and function
- Diabetes Treatment and Management
- Cancer, Hypoxia, and Metabolism
- Diet and metabolism studies
McMaster University
2015-2025
University of Guelph
2006-2015
University of Lincoln
2015
Cleveland Clinic
2007
Exercise training induces mitochondrial biogenesis, but the time course of molecular sequelae that accompany repetitive stimuli remains to be determined in human skeletal muscle. Therefore, throughout a seven-session, high-intensity interval period increased (12%), we examined responses (a) biogenesis and fusion fission proteins, (b) selected transcriptional mRNAs proteins Muscle biopsies were obtained 4 24 h after 1st, 3rd, 5th 7th session. PGC-1α mRNA was >10-fold 1st session returned...
Caloric restriction that promotes weight loss is an effective strategy for treating non-alcoholic fatty liver disease and improving insulin sensitivity in people with type 2 diabetes1. Despite its effectiveness, most individuals, usually not maintained partly due to physiological adaptations suppress energy expenditure, a process known as adaptive thermogenesis, the mechanistic underpinnings of which are unclear2,3. Treatment rodents fed high-fat diet recombinant growth differentiating...
PGC-1alpha overexpression in skeletal muscle, vivo, has yielded disappointing and unexpected effects, including disrupted cellular integrity insulin resistance. These unanticipated results may stem from an excessive transgenic animals. Therefore, we examined the effects of a modest single rat on fuel-handling proteins sensitivity. We also whether selectively targeted subsarcolemmal (SS) mitochondrial fatty acid oxidation, because SS mitochondria are metabolically more plastic than...
In selected mammalian tissues, long chain fatty acid transporters (FABPpm, FAT/CD36, FATP1, and FATP4) are co-expressed. There is controversy as to whether they all function membrane-bound channel acids oxidation and/or esterification. Among skeletal muscles, the protein expression of FABPpm, FATP4, but not correlated highly with capacities for oxidative metabolism (r>or=0.94), (r>or=0.88), triacylglycerol esterification (r>or=0.87). We overexpressed independently within a normal physiologic...
Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines evidence show these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise numerous health benefits, there no it affects or endocrine muscle-to-skin signaling occurs. We demonstrate endurance attenuates age-associated in humans mice identify exercise-induced IL-15 as novel regulator function aging...
Statins reduce lipid levels and are widely prescribed. have been associated with an increased incidence of type 2 diabetes, but the mechanisms unclear. Activation NOD-like receptor family, pyrin domain containing 3 (NLRP3)/caspase-1 inflammasome, promotes insulin resistance, a precursor diabetes. We showed that four different statins interleukin-1β (IL-1β) secretion from macrophages, which is characteristic NLRP3 inflammasome activation. This effect was dose dependent, absent in NLRP3−/−...
Abstract Obesity results from a caloric imbalance between energy intake, absorption and expenditure. In both rodents humans, diet-induced thermogenesis contributes to expenditure involves the activation of brown adipose tissue (BAT). We hypothesize that environmental toxicants commonly used as food additives or pesticides might reduce BAT through suppression uncoupling protein 1 (UCP1) this may contribute development obesity. Using step-wise screening approach, we discover organophosphate...
Type 2 diabetes and obesity increase the risk of developing colorectal cancer. Metformin may reduce cancer but mechanisms mediating this effect remain unclear. In mice humans, a high-fat diet (HFD), metformin are known to alter gut microbiome whether is important for influencing tumor growth not known. Mice with syngeneic MC38 colon adenocarcinomas were treated or feces obtained from control mice. We find that compared chow-fed controls, increased when fed HFD acceleration can be partially...
Intramuscular triacylglycerol (IMTG) accumulation in obesity has been attributed to increased fatty acid transport and/or alterations mitochondrial oxidation. Alternatively, an imbalance these two processes may channel acids into storage. Therefore, red and white muscles of lean obese Zucker rats, we examined whether the increase IMTG was attributable rate rather than subsarcolemmal (SS) or intermyofibrillar (IMF) In animals selected parameters were upregulated, including palmitate (red:...
Deacetylation of PGC-1alpha by SIRT1 is thought to be an important step in increasing transcriptional activity, since muscle cell lines induces protein expression and mitochondrial biogenesis. We examined the relationship between markers density, (a) across a range metabolically heterogeneous skeletal muscles heart, when biogenesis was stimulated (b) chronic stimulation (7 days) (c) AICAR administration (5 days), finally, (d) we also effects overexpression on PGC-1alpha. activity were...
Calcium/calmodulin-dependent protein kinase (CaMK) activation induces mitochondrial biogenesis in response to increasing cytosolic calcium concentrations. Calcium leak from the ryanodine receptor (RyR) is regulated by reactive oxygen species (ROS), which increased with high-fat feeding. We examined whether ROS-induced CaMKII-mediated signaling induced skeletal muscle selected models of lipid oversupply. In obese Zucker rats and high-fat-fed rodents, content was upregulated, CaMKII...
AMP-activated protein kinase (AMPK) is thought to be a central player in regulating myocardial metabolism and its activation has been shown inhibit cardiac hypertrophy. Recently, mice with muscle-specific deletion of AMPK β1/β2 subunits (AMPKβ1β2-deficient mice, β1β2M-KO) have generated possess <10% normal activity muscle. However, how/if dramatic deficiency alters metabolism, function, or morphology not investigated. Therefore, the aim this study was determine whether significant loss...
We have examined the effects of administration testosterone for 7 days on monocarboxylate transporter (MCT) 1 and MCT4 mRNAs proteins in seven metabolically heterogeneous rat hindlimb muscles heart. In addition, we also treatment plasmalemmal MCT1 MCT4, lactate transport into giant sarcolemmal vesicles prepared from red white Testosterone did not alter or mRNA, except plantaris muscle. increased (20%-77%, P < 0.05) protein (29%-110%, P< five out examined. contrast, heart was (P> 0.05), MCT 4...
Increased liver de novo lipogenesis (DNL) is a hallmark of nonalcoholic steatohepatitis (NASH). A key enzyme controlling DNL upregulated in NASH ATP citrate lyase (ACLY). In mice, inhibition ACLY reduces steatosis, ballooning, and fibrosis inhibits activation hepatic stellate cells. Glucagon-like peptide-1 receptor (GLP-1R) agonists lower body mass, insulin resistance, steatosis without improving fibrosis. Here, we find that combining an inhibitor ACLY, bempedoic acid, the GLP-1R agonist...
Sodium-glucose cotransporter 2 inhibitors such as canagliflozin lower blood glucose and reduce cardiovascular events in people with type diabetes through mechanisms that are not fully understood. Canagliflozin has been shown to increase the activity of AMP-activated protein kinase (AMPK), a metabolic energy sensor important for increasing fatty acid oxidation expenditure suppressing lipogenesis inflammation, but whether AMPK activation is mediating some beneficial effects determined. We,...
In skeletal muscle, mitochondria exist as two subcellular populations known subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. SS preferentially respond to exercise training, suggesting divergent transcriptional control of the mitochondrial genomes. The co-activator peroxisome proliferator-activated receptor γ 1α (PGC-1α) transcription factor A (Tfam) have been implicated in direct regulation genome mice, although IMF differences may exist, potential signalling events regulating...
Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 a complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was examine whether treatment improves insulin sensitivity capacity obese resistant mice skeletal mediating potential effects.Glucose sensitivity, capacity, electron transport chain content/activity were examined wildtype (WT) β1β2...