ORCID Profile
0000-0003-3867-8901
Current Organisation
University of British Columbia
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Publisher: Wiley
Date: 12-07-2021
DOI: 10.1113/JP281774
Abstract: Ambient cold exposure is often regarded as a promising anti‐obesity treatment in mice. However, most preclinical studies aimed at treating obesity via cold‐induced thermogenesis have been confounded by subthermoneutral housing temperatures. Therefore, the ability of ambient cold to combat diet‐induced obesity in mice housed under humanized thermoneutral conditions is currently unknown. Moreover, mammals such as mice are rarely exposed to chronic ambient cold without reprieve, yet mice are often subjected to experimental conditions of chronic rather than intermittent cold exposure (ICE), despite ICE being more physiologically relevant. In the present study, we provide novel evidence that thermoneutral housing uncouples the effects of ICE on glucose and energy homeostasis suggesting that ICE, despite improving glucose tolerance, is not an effective obesity treatment when mice are housed under humanized thermoneutral conditions. The present study examines whether a physiologically relevant model of ambient cold exposure, intermittent cold exposure (ICE), could ameliorate the metabolic impairments of diet‐induced obesity in male and female mice housed under humanized thermoneutral conditions. Male and female C57BL/6J mice housed at thermoneutrality (29°C) were fed a low‐fat diet or high‐fat diet for 6 weeks before being weight matched into groups that remained unperturbed or underwent ICE for 4 weeks (4°C for 60 min day –1 5 days week –1 ) when being maintained on their respective diets. ICE induced rapid and persistent hyperphagia exacerbating rather than attenuating high‐fat diet‐induced obesity over time. These ICE‐induced increases in adiposity were found to be energy intake‐dependent via pair‐feeding. Despite exacerbating high‐fat diet‐induced obesity, ICE improved glucose tolerance, independent of diet, in a sex‐specific manner. The effects of ICE on glucose tolerance were not attributed to improvements in whole‐body insulin tolerance, tissue specific insulin action, nor differences in markers of hepatic insulin clearance or pancreatic beta cell proliferation. Instead, ICE increased serum concentrations of insulin and C‐peptide in response to glucose, suggesting that ICE may improve glucose tolerance by potentiating pancreatic glucose‐stimulated insulin secretion. These data suggest that ICE, despite improving glucose tolerance, is not an effective obesity treatment in mice housed under humanized conditions.
Publisher: Wiley
Date: 20-09-2013
DOI: 10.1002/OBY.20605
Abstract: PGC‐1α is a transcriptional co‐activator and master regulator of mitochondrial biogenesis. While extensively studied in skeletal and cardiac muscle, recent findings suggest that white adipose tissue PGC‐1α plays an important role in regulating glucose homeostasis. The purpose of the present investigation was to evaluate the role of AMPK in regulating PGC‐1α and mitochondrial enzymes in mouse epididymal and inguinal subcutaneous adipose tissue. Mitochondrial protein content and norepinephrine and CL 316,243‐induced PGC‐1α mRNA expression were studied in mouse epididymal and inguinal adipose tissue from wild‐type and AMPK β1 −/− mice. The protein content and phosphorylation of AMPKα was reduced in epididymal adipose tissue from AMPK β1 −/− compared to WT mice, concomitant with decreases in PGC‐1α and mitochondrial marker proteins. Norepinephrine and CL 316,243‐mediated induction of PGC‐1α were decreased in cultured epididymal adipose tissue from AMPK β1 −/− relative to WT mice. In inguinal adipose tissue from AMPK β1 −/− mice, mitochondrial marker protein content and norepinephrine and CL 316,243‐mediated increases in PGC‐1α were normal despite reductions in the content and phosphorylation of AMPKα. Norepinephrine‐ and CL 316,243‐mediated induction of PGC‐1α and mitochondrial protein expression is regulated by AMPK in epididymal, but not inguinal adipose tissue.
Publisher: Oxford University Press (OUP)
Date: 2022
Abstract: Within brown adipose tissue (BAT), the brain isoform of creatine kinase (CKB) has been proposed to regulate the regeneration of ADP and phosphocreatine in a futile creatine cycle (FCC) that stimulates energy expenditure. However, the presence of FCC, and the specific creatine kinase isoforms regulating this theoretical model within white adipose tissue (WAT), remains to be fully elucidated. In the present study, creatine did not stimulate respiration in cultured adipocytes, isolated mitochondria or mouse permeabilized WAT. Additionally, while creatine kinase ubiquitous-type, mitochondrial (CKMT1) mRNA and protein were detected in human WAT, shRNA-mediated reductions in Ckmt1 did not decrease submaximal respiration in cultured adipocytes, and ablation of CKMT1 in mice did not alter energy expenditure, mitochondrial responses to pharmacological β3-adrenergic activation (CL 316, 243) or exacerbate the detrimental metabolic effects of consuming a high-fat diet. Taken together, these findings solidify CKMT1 as dispensable in the regulation of energy expenditure, and unlike in BAT, they do not support the presence of FCC within WAT.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.PSYNEUEN.2017.05.005
Abstract: To determine if glucagon is involved in mediating the increase in blood glucose levels caused by the second-generation antipsychotic drug olanzapine. Whole body glucagon receptor deficient mice (Gcgr Olanzapine treatment increased serum glucagon and lead to rapid increases in blood glucose concentrations in WT mice. Gcgr Gcgr
Publisher: American Physiological Society
Date: 05-2013
DOI: 10.1152/JAPPLPHYSIOL.00946.2012
Abstract: Interleukin-6 (IL-6) increases glucose uptake in resting skeletal muscle. IL-6 is released from skeletal muscle during exercise however it is not known whether this IL-6 response is important for exercise-induced increases in skeletal muscle glucose uptake. We report that IL-6 knockout (KO) mice, 4 mo of age, have similar body weight to wild-type (WT), and, under resting conditions, oxygen consumption, food intake, substrate utilization, glucose tolerance, and insulin sensitivity are not different. Maximal exercise capacity is also similar to WT. We investigated substrate utilization and glucose clearance in vivo during steady-state treadmill running at 70% of maximal running speed and found that WT and IL-6 KO mice had similar rates of substrate utilization, muscle glucose clearance, and phosphorylation of AMP-activated protein kinase T172. These data provide evidence that IL-6 does not play a major role in regulating substrate utilization or skeletal muscle glucose uptake during steady-state endurance exercise.
Publisher: Frontiers Media SA
Date: 19-07-2016
Location: United States of America
Location: No location found
No related grants have been discovered for David Wright.