Susceptibility to diet-induced obesity at thermoneutral conditions is independent of UCP1

TY - JOUR

T1 - Susceptibility to diet-induced obesity at thermoneutral conditions is independent of UCP1

AU - Dieckmann, Sebastian

AU - Strohmeyer, Akim

AU - Willershäuser, Monja

AU - Maurer, Stefanie F

AU - Wurst, Wolfgang

AU - Marschall, Susan

AU - de Angelis, Martin Hrabe

AU - Kühn, Ralf

AU - Worthmann, Anna

AU - Fuh, Marceline M

AU - Heeren, Joerg

AU - Köhler, Nikolai

AU - Pauling, Josch K

AU - Klingenspor, Martin

PY - 2022/2/1

Y1 - 2022/2/1

N2 - Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high-caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. UCP1 knockout and wild-type mice were housed at 30°C and fed a control diet for 4 wk followed by 8 wk of high-fat diet. Body weight and food intake were monitored continuously over the course of the study, and indirect calorimetry was used to determine energy expenditure during both feeding periods. Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake, and energy expenditure were not affected by loss of UCP1 function during both feeding periods. We introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages. Our results demonstrate that UCP1 does not protect against diet-induced obesity at thermoneutrality.NEW & NOTEWORTHY We provide evidence that the abundance of UCP1 does not influence energy metabolism at thermoneutrality studying a novel Cre-mediated UCP1-KO mouse model. This model will be a foundation for a better understanding of the contribution of UCP1 in different cell types or life stages to energy metabolism.

AB - Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high-caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. UCP1 knockout and wild-type mice were housed at 30°C and fed a control diet for 4 wk followed by 8 wk of high-fat diet. Body weight and food intake were monitored continuously over the course of the study, and indirect calorimetry was used to determine energy expenditure during both feeding periods. Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake, and energy expenditure were not affected by loss of UCP1 function during both feeding periods. We introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages. Our results demonstrate that UCP1 does not protect against diet-induced obesity at thermoneutrality.NEW & NOTEWORTHY We provide evidence that the abundance of UCP1 does not influence energy metabolism at thermoneutrality studying a novel Cre-mediated UCP1-KO mouse model. This model will be a foundation for a better understanding of the contribution of UCP1 in different cell types or life stages to energy metabolism.

KW - Adipose Tissue, Brown/metabolism

KW - Animals

KW - Calorimetry, Indirect/methods

KW - Diet, High-Fat/adverse effects

KW - Disease Susceptibility/metabolism

KW - Eating/genetics

KW - Energy Metabolism/genetics

KW - Female

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Obesity/etiology

KW - Temperature

KW - Thermogenesis/genetics

KW - Uncoupling Protein 1/genetics

KW - Weight Gain/genetics

U2 - 10.1152/ajpendo.00278.2021

DO - 10.1152/ajpendo.00278.2021

M3 - SCORING: Journal article

C2 - 34927460

VL - 322

SP - E85-E100

JO - AM J PHYSIOL-ENDOC M

JF - AM J PHYSIOL-ENDOC M

SN - 0193-1849

IS - 2

ER -