Short-term thermoneutral housing alters glucose metabolism and markers of adipose tissue browning in response to a high-fat diet in lean mice

May 24, 2018American journal of physiology. Regulatory, integrative and comparative physiology

Short-term neutral temperature housing changes blood sugar and fat tissue browning in lean mice on a high-fat diet

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Abstract

Glucose intolerance was observed after 1 or 5 days of a high-fat diet in mice, regardless of housing temperature.

Reduced glucose uptake in brown fat occurred at 22°C, while reduced glucose uptake in leg muscles was noted at 30°C.
Fasting glucose levels, food intake, and energy expenditure were significantly lower at 30°C, independent of diet.
Markers of fat cell browning decreased in brown fat and subcutaneous fat at 30°C, but not in abdominal fat.
Housing temperature significantly influences the cellular pathways regulating glucose tolerance during acute high-fat diet exposure.
Short-term changes in housing temperature should be considered when interpreting metabolic studies in mice.

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Systemic insulin resistance and glucose intolerance occur with as little as 3 days of a high-fat diet (HFD) in mice and humans; the mechanisms that initiate acute insulin resistance are unknown. Most laboratories house mice at 22°C, which is below their thermoneutral temperature (~30°C). Cold stress has been shown to increase white adipose tissue (WAT) browning, alter lipid trafficking, and impair immune function, whereas energy intake and expenditure decrease with increasing ambient temperature; importantly, dysregulation of these parameters has been strongly linked to obesity-induced insulin resistance. Therefore, we compared acute changes in glucose metabolism and the metabolic phenotype in lean mice in response to a control diet or HFD housed at standard vivarium (22°C) and thermoneutral (30°C) temperatures. Glucose intolerance occurred following 1 or 5 days of HFD and was independent of housing temperature or adiposity; however, the reduction in tissue-specific glucose clearance with HFD diverged by temperature with reduced brown adipose tissue (BAT) glucose uptake at 22°C but reduced soleus glucose uptake at 30°C. Fasting glucose, food intake, and energy expenditure were significantly lower at 30°C, independent of diet. Additionally, markers of browning in both BAT and inguinal subcutaneous WAT, but not perigonadal epididymal WAT, decreased at 30°C. Together, we find housing temperature has a significant impact on the cellular pathways that regulate glucose tolerance in response to an acute HFD exposure. Thus, even short-term changes in housing temperature should be highly considered in interpretation of metabolic studies in mice.

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Short-term thermoneutral housing alters glucose metabolism and markers of adipose tissue browning in response to a high-fat diet in lean mice

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