Faculty Collaboration Database

Circadian Misalignment of the 24-hour Profile of Endocannabinoid 2-Arachidonoylglycerol (2-AG) in Obese Adults. J Clin Endocrinol Metab 2020 Mar 01;105(3):792-802

Date

01/24/2020

Pubmed ID

31970413

Pubmed Central ID

PMC7015463

DOI

10.1210/clinem/dgaa028

Scopus ID

2-s2.0-85079347809 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

CONTEXT: The endocannabinoid (eCB) system partly controls hedonic eating, a major cause of obesity. While some studies suggested an overactivation of the eCB system in obesity, peripheral levels of eCBs across the 24-hour cycle have not been characterized in obese individuals despite the fact that in lean adults, levels of the eCB 2-arachidonoylglycerol (2-AG) vary across the day.

OBJECTIVE: We sought to examine 24-hour profiles of serum concentrations of 2-AG in healthy obese and nonobese adults, under well-controlled laboratory conditions. We also simultaneously assessed 24-hour profiles of 2-oleoylglycerol (2-OG), leptin, and cortisol in each participant.

DESIGN: With fixed light-dark and sleep-wake cycles, blood sampling was performed over an entire 24-hour period, including identical meals at 0900, 1400, and 1900.

PARTICIPANTS: Twelve obese (8 women, mean body mass index [BMI]: 39.1 kg/m2) and 15 nonobese (6 women; mean BMI: 23.6 kg/m2) healthy adults were studied.

RESULTS: We observed a 24-hour variation of 2-AG levels in obese individuals but, relative to nonobese adults, the amplitude was dampened and the timings of the nadir and peak were delayed by 4 to 5 hours. The profile of 2-OG was similarly misaligned. In contrast, when expressed relative to the 24-hour mean level, the 24-hour rhythm of cortisol and leptin were similar in obese and nonobese participants.

CONCLUSIONS: Obesity appears to be associated with a dampening and delay of the 24-hour variation of eCB activity relative to the central circadian signal as well as to the daily leptin rhythm. This misalignment may play a role in the pathophysiology of obesity.

Author List

Hanlon EC, Leproult R, Stuhr KL, Doncheck EM, Hillard CJ, Van Cauter E

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Arachidonic Acids
Case-Control Studies
Circadian Rhythm
Endocannabinoids
Female
Glycerides
Humans
Hydrocortisone
Leptin
Male
Obesity
Young Adult