Biomarkers of browning of white adipose tissue and their regulation during exercise- And diet-induced weight loss

TY - JOUR

T1 - Biomarkers of browning of white adipose tissue and their regulation during exercise- And diet-induced weight loss

AU - Nakhuda, Asif

AU - Josse, Andrea R.

AU - Gburcik, Valentina

AU - Crossland, Hannah

AU - Raymond, Frederic

AU - Metairon, Sylviane

AU - Good, Liam

AU - Atherton, Philip J.

AU - Phillips, Stuart M.

AU - Timmons, James A.

PY - 2016/9

Y1 - 2016/9

N2 - Background: A hypothesis exists whereby an exercise- or dietaryinduced negative energy balance reduces human subcutaneous white adipose tissue (scWAT) mass through the formation of brown-like adipocyte (brite) cells. However, the validity of biomarkers of brite formation has not been robustly evaluated in humans, and clinical data that link brite formation and weight loss are sparse. Objectives: We used rosiglitazone and primary adipocytes to stringently evaluate a set of biomarkers for brite formation and determined whether the expression of biomarker genes in scWAT could explain the change in body composition in response to exercise training combined with calorie restriction in obese and overweight women (n = 79). Design: Gene expression was derived from exon DNA microarrays and preadipocytes from obesity-resistant and -sensitive mice treated with rosiglitazone to generate candidate brite biomarkers from a microarray. These biomarkers were evaluated against data derived from scWAT RNA from obese and overweight women before and after supervised exercise 5 d/wk for 16 wk combined with modest calorie restriction (w0.84 MJ/d). Results: Forty percent of commonly used brite gene biomarkers exhibited an exon or strain-specific regulation. No biomarkers were positively related to weight loss in human scWAT. Greater weight loss was significantly associated with less uncoupling protein 1 expression (P = 0.006, R2 = 0.09). In a follow-up global analysis, there were 161 genes that covaried with weight loss that were linked to greater CCAAT/enhancer binding protein a activity (z = 2.0, P = 6.6 3 1027), liver X receptor a/b agonism (z = 2.1, P = 2.8 3 1027), and inhibition of leptin-like signaling (z = 22.6, P = 3.9 3 1025). Conclusion: We identify a subset of robust RNA biomarkers for brite formation and show that calorie-restriction-mediated weight loss in women dynamically remodels scWAT to take on a more-white rather than a morebrown adipocyte phenotype. Am J Clin Nutr 2016;104:557-65.

AB - Background: A hypothesis exists whereby an exercise- or dietaryinduced negative energy balance reduces human subcutaneous white adipose tissue (scWAT) mass through the formation of brown-like adipocyte (brite) cells. However, the validity of biomarkers of brite formation has not been robustly evaluated in humans, and clinical data that link brite formation and weight loss are sparse. Objectives: We used rosiglitazone and primary adipocytes to stringently evaluate a set of biomarkers for brite formation and determined whether the expression of biomarker genes in scWAT could explain the change in body composition in response to exercise training combined with calorie restriction in obese and overweight women (n = 79). Design: Gene expression was derived from exon DNA microarrays and preadipocytes from obesity-resistant and -sensitive mice treated with rosiglitazone to generate candidate brite biomarkers from a microarray. These biomarkers were evaluated against data derived from scWAT RNA from obese and overweight women before and after supervised exercise 5 d/wk for 16 wk combined with modest calorie restriction (w0.84 MJ/d). Results: Forty percent of commonly used brite gene biomarkers exhibited an exon or strain-specific regulation. No biomarkers were positively related to weight loss in human scWAT. Greater weight loss was significantly associated with less uncoupling protein 1 expression (P = 0.006, R2 = 0.09). In a follow-up global analysis, there were 161 genes that covaried with weight loss that were linked to greater CCAAT/enhancer binding protein a activity (z = 2.0, P = 6.6 3 1027), liver X receptor a/b agonism (z = 2.1, P = 2.8 3 1027), and inhibition of leptin-like signaling (z = 22.6, P = 3.9 3 1025). Conclusion: We identify a subset of robust RNA biomarkers for brite formation and show that calorie-restriction-mediated weight loss in women dynamically remodels scWAT to take on a more-white rather than a morebrown adipocyte phenotype. Am J Clin Nutr 2016;104:557-65.

KW - Browning

KW - Exercise

KW - Microarray

KW - Obesity

KW - Weight loss

KW - White adipose tissue

UR - http://www.scopus.com/inward/record.url?scp=84985961242&partnerID=8YFLogxK

U2 - 10.3945/ajcn.116.132563

DO - 10.3945/ajcn.116.132563

M3 - Article

AN - SCOPUS:84985961242

SN - 0002-9165

VL - 104

SP - 557

EP - 565

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 3

ER -