White Adipose Tissue Depots Respond to Chronic Beta-3 Adrenergic Receptor Activation in a Sexually Dimorphic and Depot Divergent Manner

Beta-3 adrenergic receptor activation via exercise or CL316,243 (CL) induces white adipose tissue (WAT) browning, improves glucose tolerance, and reduces visceral adiposity. Our aim was to determine if sex or adipose tissue depot differences exist in response to CL. Daily CL injections were administ...

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Main Authors: Eric D. Queathem, Rebecca J. Welly, Laura M. Clart, Candace C. Rowles, Hunter Timmons, Maggie Fitzgerald, Peggy A. Eichen, Dennis B. Lubahn, Victoria J. Vieira-Potter
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/12/3453
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author Eric D. Queathem
Rebecca J. Welly
Laura M. Clart
Candace C. Rowles
Hunter Timmons
Maggie Fitzgerald
Peggy A. Eichen
Dennis B. Lubahn
Victoria J. Vieira-Potter
author_facet Eric D. Queathem
Rebecca J. Welly
Laura M. Clart
Candace C. Rowles
Hunter Timmons
Maggie Fitzgerald
Peggy A. Eichen
Dennis B. Lubahn
Victoria J. Vieira-Potter
author_sort Eric D. Queathem
collection DOAJ
description Beta-3 adrenergic receptor activation via exercise or CL316,243 (CL) induces white adipose tissue (WAT) browning, improves glucose tolerance, and reduces visceral adiposity. Our aim was to determine if sex or adipose tissue depot differences exist in response to CL. Daily CL injections were administered to diet-induced obese male and female mice for two weeks, creating four groups: male control, male CL, female control, and female CL. These groups were compared to determine the main and interaction effects of sex (S), CL treatment (T), and WAT depot (D). Glucose tolerance, body composition, and energy intake and expenditure were assessed, along with perigonadal (PGAT) and subcutaneous (SQAT) WAT gene and protein expression. CL consistently improved glucose tolerance and body composition. Female PGAT had greater protein expression of the mitochondrial uncoupling protein 1 (UCP1), while SQAT (S, <i>p</i> < 0.001) was more responsive to CL in increasing UCP1 (S×T, <i>p</i> = 0.011) and the mitochondrial biogenesis induction protein, PPARγ coactivator 1α (PGC1α) (S×T, <i>p</i> = 0.026). Females also displayed greater mitochondrial OXPHOS (S, <i>p</i> < 0.05) and adiponectin protein content (S, <i>p</i> < 0.05). On the other hand, male SQAT was more responsive to CL in increasing protein levels of PGC1α (S×T, <i>p</i> = 0.046) and adiponectin (S, <i>p</i> < 0.05). In both depots and in both sexes, CL significantly increased estrogen receptor beta (ERβ) and glucose-related protein 75 (GRP75) protein content (T, <i>p</i> < 0.05). Thus, CL improves systemic and adipose tissue-specific metabolism in both sexes; however, sex differences exist in the WAT-specific effects of CL. Furthermore, across sexes and depots, CL affects estrogen signaling by upregulating ERβ.
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spelling doaj.art-8c10d61e01b049f29c8f9791293798a92023-11-23T07:38:00ZengMDPI AGCells2073-44092021-12-011012345310.3390/cells10123453White Adipose Tissue Depots Respond to Chronic Beta-3 Adrenergic Receptor Activation in a Sexually Dimorphic and Depot Divergent MannerEric D. Queathem0Rebecca J. Welly1Laura M. Clart2Candace C. Rowles3Hunter Timmons4Maggie Fitzgerald5Peggy A. Eichen6Dennis B. Lubahn7Victoria J. Vieira-Potter8Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADepartment of Biochemistry, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USABeta-3 adrenergic receptor activation via exercise or CL316,243 (CL) induces white adipose tissue (WAT) browning, improves glucose tolerance, and reduces visceral adiposity. Our aim was to determine if sex or adipose tissue depot differences exist in response to CL. Daily CL injections were administered to diet-induced obese male and female mice for two weeks, creating four groups: male control, male CL, female control, and female CL. These groups were compared to determine the main and interaction effects of sex (S), CL treatment (T), and WAT depot (D). Glucose tolerance, body composition, and energy intake and expenditure were assessed, along with perigonadal (PGAT) and subcutaneous (SQAT) WAT gene and protein expression. CL consistently improved glucose tolerance and body composition. Female PGAT had greater protein expression of the mitochondrial uncoupling protein 1 (UCP1), while SQAT (S, <i>p</i> < 0.001) was more responsive to CL in increasing UCP1 (S×T, <i>p</i> = 0.011) and the mitochondrial biogenesis induction protein, PPARγ coactivator 1α (PGC1α) (S×T, <i>p</i> = 0.026). Females also displayed greater mitochondrial OXPHOS (S, <i>p</i> < 0.05) and adiponectin protein content (S, <i>p</i> < 0.05). On the other hand, male SQAT was more responsive to CL in increasing protein levels of PGC1α (S×T, <i>p</i> = 0.046) and adiponectin (S, <i>p</i> < 0.05). In both depots and in both sexes, CL significantly increased estrogen receptor beta (ERβ) and glucose-related protein 75 (GRP75) protein content (T, <i>p</i> < 0.05). Thus, CL improves systemic and adipose tissue-specific metabolism in both sexes; however, sex differences exist in the WAT-specific effects of CL. Furthermore, across sexes and depots, CL affects estrogen signaling by upregulating ERβ.https://www.mdpi.com/2073-4409/10/12/3453adrenergic activitybrowninginsulin resistancesex differencesUCP1estrogen signaling
spellingShingle Eric D. Queathem
Rebecca J. Welly
Laura M. Clart
Candace C. Rowles
Hunter Timmons
Maggie Fitzgerald
Peggy A. Eichen
Dennis B. Lubahn
Victoria J. Vieira-Potter
White Adipose Tissue Depots Respond to Chronic Beta-3 Adrenergic Receptor Activation in a Sexually Dimorphic and Depot Divergent Manner
Cells
adrenergic activity
browning
insulin resistance
sex differences
UCP1
estrogen signaling
title White Adipose Tissue Depots Respond to Chronic Beta-3 Adrenergic Receptor Activation in a Sexually Dimorphic and Depot Divergent Manner
title_full White Adipose Tissue Depots Respond to Chronic Beta-3 Adrenergic Receptor Activation in a Sexually Dimorphic and Depot Divergent Manner
title_fullStr White Adipose Tissue Depots Respond to Chronic Beta-3 Adrenergic Receptor Activation in a Sexually Dimorphic and Depot Divergent Manner
title_full_unstemmed White Adipose Tissue Depots Respond to Chronic Beta-3 Adrenergic Receptor Activation in a Sexually Dimorphic and Depot Divergent Manner
title_short White Adipose Tissue Depots Respond to Chronic Beta-3 Adrenergic Receptor Activation in a Sexually Dimorphic and Depot Divergent Manner
title_sort white adipose tissue depots respond to chronic beta 3 adrenergic receptor activation in a sexually dimorphic and depot divergent manner
topic adrenergic activity
browning
insulin resistance
sex differences
UCP1
estrogen signaling
url https://www.mdpi.com/2073-4409/10/12/3453
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