Thermoneutral housing does not influence fat mass or glucose homeostasis in C57BL/6 mice

2018 ◽  
Vol 239 (3) ◽  
pp. 313-324 ◽  
Author(s):  
Lewin Small ◽  
Henry Gong ◽  
Christian Yassmin ◽  
Gregory J Cooney ◽  
Amanda E Brandon
Keyword(s):  
Glucose Metabolism ◽  
Ambient Temperature ◽  
Fat Mass ◽  
Glucose Homeostasis ◽  
Dietary Intervention ◽  
Whole Body ◽  
Housing Temperature ◽  
Brown Adipose ◽  
Normal Chow ◽  
Obesogenic Diet

One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collected at 22°C in mice could be influenced by animals being exposed to a chronic cold stress. The aim of this study was to investigate the effect of housing temperature on glucose homeostasis and energy metabolism of mice fed normal chow or a high-fat, obesogenic diet (HFD). Male C57BL/6J(Arc) mice were housed at standard temperature (22°C) or at thermoneutrality (29°C) and fed either chow or a 60% HFD for 13 weeks. The HFD increased fat mass and produced glucose intolerance as expected but this was not exacerbated in mice housed at thermoneutrality. Changing the ambient temperature, however, did alter energy expenditure, food intake, lipid content and glucose metabolism in skeletal muscle, liver and brown adipose tissue. Collectively, these findings demonstrate that mice regulate energy balance at different housing temperatures to maintain whole-body glucose tolerance and adiposity irrespective of the diet. Despite this, metabolic differences in individual tissues were apparent. In conclusion, dietary intervention in mice has a greater impact on adiposity and glucose metabolism than housing temperature although temperature is still a significant factor in regulating metabolic parameters in individual tissues.

scholarly journals Removal of interscapular brown adipose tissue increases aortic stiffness despite normal systemic glucose metabolism in mice

2018 ◽  
Vol 314 (4) ◽  
pp. R584-R597 ◽  
Author(s):  
Zachary I. Grunewald ◽  
Nathan C. Winn ◽  
Michelle L. Gastecki ◽  
Makenzie L. Woodford ◽  
James R. Ball ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Aortic Stiffness ◽  
Western Diet ◽  
Metabolic Function ◽  
Brown Adipose ◽  
Normal Chow

Brown adipose tissue (BAT) is considered protective against obesity and related cardiometabolic dysfunction. Indeed, activation of BAT improves glucose homeostasis and attenuates cardiovascular disease development. However, whether a reduction in BAT mass perturbs metabolic function and increases risk for cardiovascular disease remains largely unknown. To address this question, C57BL/6J male mice underwent a sham procedure or surgical bilateral excision of interscapular BAT (iBATx) and were fed a normal chow or a Western diet for 18 wk, creating four groups ( n = 10/group). Mice were housed at 25°C. As expected, the Western diet increased final body weight and adiposity; however, contrary to our hypothesis, iBATx did not potentiate adiposity independent of diet. Furthermore, iBATx did not affect indexes of glycemic control (HbA1c, fasting glucose and insulin, and glucose area under the curve during a glucose tolerance test) and produced minimal-to-no effects on lipid homeostasis. The absence of metabolic disturbances with iBATx was not attributed to regrowth of iBAT or a “browning” or proliferative compensatory response of other BAT depots. Notably, iBATx caused an increase in aortic stiffness in normal chow-fed mice only, which was associated with an increase in aortic uncoupling protein-1. Collectively, we demonstrated that, at 25°C (i.e., limited thermal stress conditions), a substantial reduction in BAT mass via iBATx does not disrupt systemic glucose metabolism, challenging the current dogma that preservation of BAT is obligatory for optimal metabolic function. However, iBATx caused aortic stiffening in lean mice, hence supporting the existence of an interplay between iBAT and aortic stiffness, independent of alterations in glucose homeostasis.

scholarly journals Brown Adipose Tissue Volume and Fat Content are Positively Associated with Whole-Body Adiposity in Young Men, Not in Women

2021 ◽  
Author(s):  
Guillermo Sanchez-Delgado ◽  
Borja Martinez-Tellez ◽  
Francisco M. Acosta ◽  
Samuel Virtue ◽  
Antonio Vidal-Puig ◽  
...  
Keyword(s):  
Young Adults ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Fat Mass ◽  
Visceral Adipose Tissue ◽  
Whole Body ◽  
Body Adiposity ◽  
Brown Adipose ◽  
Pet Ct ◽  
Visceral Adipose

<a>Human brown adipose tissue (BAT) volume has been consistently claimed as inversely associated with whole-body adiposity. However, recent advances in the assessment of human BAT suggest that previously reported associations may have been biased. The present cross-sectional study investigates the association of BAT volume, mean radiodensity, and <sup>18</sup>F-fluordeoxyglucose (<sup>18</sup>F-FDG) uptake (assessed via a static positron emission tomography-computerized tomography (PET-CT) scan after a 2-hour personalized cold exposure) with whole-body adiposity (measured by dual-energy X-ray absorptiometry) in 126 young adults (42 men / 84 women; 25±5 kg/m<sup>2</sup>). BAT volume, but not <sup>18</sup>F-FDG uptake, was positively associated with body mass index (BMI), fat mass, and visceral adipose tissue mass in men, but not in women. These associations were independent of the date when the PET-CT was performed, insulin sensitivity and body surface area. BAT mean radiodensity, an inverse proxy of BAT fat content, was negatively associated </a>was with BMI, waist circumference, fat mass and visceral adipose tissue mas in men and with percentage fat mass in women. These results refute the widely held belief that human BAT volume is reduced in obese persons, at least in young adults, and suggest that it might even be the opposite in young men.

scholarly journals Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight

2015 ◽  
Vol 113 (2) ◽  
pp. 446-451 ◽  
Author(s):  
Yong-Qi Li ◽  
Yogendra B. Shrestha ◽  
Min Chen ◽  
Tatyana Chanturiya ◽  
Oksana Gavrilova ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Energy Balance ◽  
Glucose Metabolism ◽  
Lipid Synthesis ◽  
Whole Body ◽  
Standard Diet ◽  
Fatty Acid Binding ◽  
Brown Adipose

Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsα signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight.

scholarly journals Role of brown adipose tissue in glucose utilization in conscious pre-obese Zucker rats

1989 ◽  
Vol 263 (1) ◽  
pp. 305-308 ◽  
Author(s):  
S Krief ◽  
R Bazin ◽  
F Dupuy ◽  
M Lavau
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Brown Adipose Tissue ◽  
Glucose Utilization ◽  
Whole Body ◽  
Zucker Rats ◽  
Noradrenaline Content ◽  
Metabolism Rate ◽  
Brown Adipose ◽  
The Difference

In 16-day-old conscious Zucker rats, at a time when pre-obese fa/fa rats were not yet hyperinsulinaemic compared with their lean Fa/fa littermates, the whole-body glucose-metabolism rate was decreased by 10% in pre-obese compared with lean pups. The markedly decreased glucose utilization found in brown adipose tissue (BAT) of pre-obese compared with lean pups accounted for at least 70% of the difference in whole-body glucose metabolism observed between the two genotypes. In pre-obese fa/fa rats, the 20% decrease in noradrenaline content of BAT reported in this study is consistent with the diminished glucose utilization by this tissue, and further supports the hypothesis of a defect in the sympathetic-nervous-system regulation of BAT metabolism as one of the primary causes for this genetic obesity.

scholarly journals Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans

Diabetes ◽  
2014 ◽  
Vol 63 (12) ◽  
pp. 4089-4099 ◽  
Author(s):  
M. Chondronikola ◽  
E. Volpi ◽  
E. Borsheim ◽  
C. Porter ◽  
P. Annamalai ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Whole Body ◽  
Brown Adipose

scholarly journals Astrocyte Clocks and Glucose Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Olga Barca-Mayo ◽  
Miguel López
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Circadian Clock ◽  
Glucose Homeostasis ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
Whole Body

The endogenous timekeeping system evolved to anticipate the time of the day through the 24 hours cycle of the Earth’s rotation. In mammals, the circadian clock governs rhythmic physiological and behavioral processes, including the daily oscillation in glucose metabolism, food intake, energy expenditure, and whole-body insulin sensitivity. The results from a series of studies have demonstrated that environmental or genetic alterations of the circadian cycle in humans and rodents are strongly associated with metabolic diseases such as obesity and type 2 diabetes. Emerging evidence suggests that astrocyte clocks have a crucial role in regulating molecular, physiological, and behavioral circadian rhythms such as glucose metabolism and insulin sensitivity. Given the concurrent high prevalence of type 2 diabetes and circadian disruption, understanding the mechanisms underlying glucose homeostasis regulation by the circadian clock and its dysregulation may improve glycemic control. In this review, we summarize the current knowledge on the tight interconnection between the timekeeping system, glucose homeostasis, and insulin sensitivity. We focus specifically on the involvement of astrocyte clocks, at the organism, cellular, and molecular levels, in the regulation of glucose metabolism.

scholarly journals Brown Adipose Tissue Volume and Fat Content are Positively Associated with Whole-Body Adiposity in Young Men, Not in Women

2021 ◽  
Author(s):  
Guillermo Sanchez-Delgado ◽  
Borja Martinez-Tellez ◽  
Francisco M. Acosta ◽  
Samuel Virtue ◽  
Antonio Vidal-Puig ◽  
...  
Keyword(s):  
Young Adults ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Fat Mass ◽  
Visceral Adipose Tissue ◽  
Whole Body ◽  
Body Adiposity ◽  
Brown Adipose ◽  
Pet Ct ◽  
Visceral Adipose

<a>Human brown adipose tissue (BAT) volume has been consistently claimed as inversely associated with whole-body adiposity. However, recent advances in the assessment of human BAT suggest that previously reported associations may have been biased. The present cross-sectional study investigates the association of BAT volume, mean radiodensity, and <sup>18</sup>F-fluordeoxyglucose (<sup>18</sup>F-FDG) uptake (assessed via a static positron emission tomography-computerized tomography (PET-CT) scan after a 2-hour personalized cold exposure) with whole-body adiposity (measured by dual-energy X-ray absorptiometry) in 126 young adults (42 men / 84 women; 25±5 kg/m<sup>2</sup>). BAT volume, but not <sup>18</sup>F-FDG uptake, was positively associated with body mass index (BMI), fat mass, and visceral adipose tissue mass in men, but not in women. These associations were independent of the date when the PET-CT was performed, insulin sensitivity and body surface area. BAT mean radiodensity, an inverse proxy of BAT fat content, was negatively associated </a>was with BMI, waist circumference, fat mass and visceral adipose tissue mas in men and with percentage fat mass in women. These results refute the widely held belief that human BAT volume is reduced in obese persons, at least in young adults, and suggest that it might even be the opposite in young men.

scholarly journals The PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study: Rationale, Design and Preliminary Screening Results

2021 ◽  
Vol 8 ◽  
Author(s):  
Anouk Gijbels ◽  
Inez Trouwborst ◽  
Kelly M. Jardon ◽  
Gabby B. Hul ◽  
Els Siebelink ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Dietary Intervention ◽  
Hepatic Insulin Resistance ◽  
Whole Body ◽  
Primary Study ◽  
Sensitivity Index ◽  
Tissue Specific

Background: It is well-established that the etiology of type 2 diabetes differs between individuals. Insulin resistance (IR) may develop in different tissues, but the severity of IR may differ in key metabolic organs such as the liver and skeletal muscle. Recent evidence suggests that these distinct tissue-specific IR phenotypes may also respond differentially to dietary macronutrient composition with respect to improvements in glucose metabolism.Objective: The main objective of the PERSON study is to investigate the effects of an optimal vs. suboptimal dietary macronutrient intervention according to tissue-specific IR phenotype on glucose metabolism and other health outcomes.Methods: In total, 240 overweight/obese (BMI 25 – 40 kg/m2) men and women (age 40 – 75 years) with either skeletal muscle insulin resistance (MIR) or liver insulin resistance (LIR) will participate in a two-center, randomized, double-blind, parallel, 12-week dietary intervention study. At screening, participants undergo a 7-point oral glucose tolerance test (OGTT) to determine the hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), classifying each participant as either “No MIR/LIR,” “MIR,” “LIR,” or “combined MIR/LIR.” Individuals with MIR or LIR are randomized to follow one of two isocaloric diets varying in macronutrient content and quality, that is hypothesized to be either an optimal or suboptimal diet, depending on their tissue-specific IR phenotype (MIR/LIR). Extensive measurements in a controlled laboratory setting as well as phenotyping in daily life are performed before and after the intervention. The primary study outcome is the difference in change in disposition index, which is the product of insulin sensitivity and first-phase insulin secretion, between participants who received their hypothesized optimal or suboptimal diet.Discussion: The PERSON study is one of the first randomized clinical trials in the field of precision nutrition to test effects of a more personalized dietary intervention based on IR phenotype. The results of the PERSON study will contribute knowledge on the effectiveness of targeted nutritional strategies to the emerging field of precision nutrition, and improve our understanding of the complex pathophysiology of whole body and tissue-specific IR.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03708419, clinicaltrials.gov as NCT03708419.

Prolonged β2-adrenergic agonist treatment improves glucose homeostasis in diet-induced obese UCP1-/- mice.

2021 ◽  
Author(s):  
Sten van Beek ◽  
Anastasia Kalinovich ◽  
Gert Schaart ◽  
Tore Bengtsson ◽  
Joris Hoeks
Keyword(s):  
Oxygen Consumption ◽  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Fasting Blood Glucose ◽  
Whole Body ◽  
Oral Glucose ◽  
High Fat ◽  
Insulin Tolerance ◽  
Brown Adipose ◽  
Fat Feeding

Objectives- Prolonged supplementation with the β2-agonist clenbuterol improves glucose homeostasis in diabetic rodents, likely via β2-adrenoceptor (β2-AR)-mediated effects in the skeletal muscle and liver. However, since rodents have, in contrast to- especially diabetic- humans, substantial quantities of brown adipose tissue (BAT) and clenbuterol has affinity to β1- and β3-ARs, the contribution of BAT to these improvements is unclear. Therefore, we investigated clenbuterol-mediated improvements in glucose homeostasis in uncoupling protein 1 deficient (UCP1-/-) mice, lacking thermogenic BAT, vs. wild-type (WT) mice. Methods- Anaesthetized WT and UCP1-/- C57Bl/6 mice were injected with saline or clenbuterol and whole-body oxygen consumption was measured. Furthermore, male WT and UCP1-/- C57Bl/6 mice were subjected to 17-weeks of chow feeding, high-fat feeding or high-fat feeding with clenbuterol treatment between week 13-17. Body composition was measured weekly with MRI. Oral glucose tolerance and insulin tolerance tests were performed in week 15 and 17, respectively. Results- Clenbuterol increased oxygen consumption ~2-fold in WT mice. This increase was blunted in UCP1-/- mice, indicating clenbuterol-mediated activation of BAT thermogenesis. High-fat feeding induced diabetogenic phenotypes in both genotypes. However, 2-weeks clenbuterol treatment significantly reduced fasting blood glucose by 12.9% in WT and 14.8% in UCP1-/- mice. Clenbuterol treatment improved glucose and insulin tolerance in both genotypes compared to HFD controls and normalized to chow-fed control mice independent of body mass and -composition alterations. Conclusions- Clenbuterol improved whole-body glucose homeostasis independent of UCP1. Given the low human abundancy of BAT, β2-agonist treatment provides a potential novel route for glucose disposal in diabetic humans.

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