Increased plasma fatty acid clearance, not fatty acid concentration, is associated with muscle insulin resistance in people with obesity.
Adipose tissue
Fatty acids
Insulin resistance
Obesity
Journal
Metabolism: clinical and experimental
ISSN: 1532-8600
Titre abrégé: Metabolism
Pays: United States
ID NLM: 0375267
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
14
03
2022
revised:
24
04
2022
accepted:
10
05
2022
pubmed:
17
5
2022
medline:
9
6
2022
entrez:
16
5
2022
Statut:
ppublish
Résumé
Although it is well-accepted that increased plasma free fatty acid (FFA) concentration causes lipid overload and muscle insulin resistance in people with obesity, plasma FFA concentration poorly predicts insulin-resistant glucose metabolism. It has been proposed that hyperinsulinemia in people with obesity sufficiently inhibits adipose tissue triglyceride lipolysis to prevent FFA-induced insulin resistance. However, we hypothesized enhanced FFA clearance in people with obesity, compared with lean people, prevents a marked increase in plasma FFA even when FFA appearance is high. We assessed FFA kinetics during basal conditions and during a hyperinsulinemic-euglycemic clamp procedure in 14 lean people and 46 people with obesity by using [ Plasma FFA clearance was accelerated in participants with obesity and correlated negatively with muscle insulin sensitivity without a difference between lean and obese participants. Furthermore, insulin infusion increased FFA clearance and the increase was greater in obese than lean participants. Our findings suggest plasma FFA extraction efficiency, not just plasma FFA concentration, is an important determinant of the cellular fatty acid load and the stimulatory effect of insulin on FFA clearance counteracts some of its antilipolytic effect.
Sections du résumé
BACKGROUND
Although it is well-accepted that increased plasma free fatty acid (FFA) concentration causes lipid overload and muscle insulin resistance in people with obesity, plasma FFA concentration poorly predicts insulin-resistant glucose metabolism. It has been proposed that hyperinsulinemia in people with obesity sufficiently inhibits adipose tissue triglyceride lipolysis to prevent FFA-induced insulin resistance. However, we hypothesized enhanced FFA clearance in people with obesity, compared with lean people, prevents a marked increase in plasma FFA even when FFA appearance is high.
METHODS
We assessed FFA kinetics during basal conditions and during a hyperinsulinemic-euglycemic clamp procedure in 14 lean people and 46 people with obesity by using [
RESULTS
Plasma FFA clearance was accelerated in participants with obesity and correlated negatively with muscle insulin sensitivity without a difference between lean and obese participants. Furthermore, insulin infusion increased FFA clearance and the increase was greater in obese than lean participants.
CONCLUSIONS
Our findings suggest plasma FFA extraction efficiency, not just plasma FFA concentration, is an important determinant of the cellular fatty acid load and the stimulatory effect of insulin on FFA clearance counteracts some of its antilipolytic effect.
Identifiants
pubmed: 35577100
pii: S0026-0495(22)00094-4
doi: 10.1016/j.metabol.2022.155216
pmc: PMC10424797
mid: NIHMS1920128
pii:
doi:
Substances chimiques
Fatty Acids
0
Fatty Acids, Nonesterified
0
Insulin
0
Glucose
IY9XDZ35W2
Banques de données
ClinicalTrials.gov
['NCT02994459', 'NCT03408613']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
155216Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK115400
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056341
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK131188
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020579
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002345
Pays : United States
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
Références
J Physiol Pharmacol. 2008 Mar;59(1):77-83
pubmed: 18441389
Am J Physiol Endocrinol Metab. 2001 Sep;281(3):E600-7
pubmed: 11500316
Diabetes. 2003 Jul;52(7):1641-8
pubmed: 12829627
Exp Biol Med (Maywood). 2010 Apr;235(4):514-21
pubmed: 20407084
J Lipid Res. 2018 Jul;59(7):1084-1093
pubmed: 29627764
Diabetes. 2011 Oct;60(10):2441-9
pubmed: 21948998
Physiol Rev. 2018 Oct 1;98(4):2133-2223
pubmed: 30067154
Diabetes. 2001 Jun;50(6):1389-96
pubmed: 11375340
Diabetes. 2011 Jan;60(1):47-55
pubmed: 20943748
Dev Cell. 2002 Apr;2(4):477-88
pubmed: 11970897
Clin Sci (Lond). 1989 Dec;77(6):663-70
pubmed: 2691176
Diabetes Care. 2012 Jun;35(6):1316-21
pubmed: 22474039
J Biol Chem. 2008 May 16;283(20):13578-85
pubmed: 18353783
FASEB J. 2004 Jul;18(10):1144-6
pubmed: 15132977
Obes Facts. 2015;8(2):147-55
pubmed: 25895754
Diabetologia. 2018 Apr;61(4):821-830
pubmed: 29275428
Diabetes. 2002 May;51(5):1477-84
pubmed: 11978645
Diabetologia. 2006 Jan;49(1):149-57
pubmed: 16323003
Am J Physiol Endocrinol Metab. 2021 Apr 1;320(4):E653-E670
pubmed: 33522398
Am J Physiol. 1992 Jul;263(1 Pt 1):E79-84
pubmed: 1636701
Am J Physiol Endocrinol Metab. 2000 Nov;279(5):E1072-9
pubmed: 11052962
Diabetes. 2020 Oct;69(10):2112-2119
pubmed: 32651241
Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E785-96
pubmed: 21750264
Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15430-5
pubmed: 19706383
Annu Rev Nutr. 2002;22:383-415
pubmed: 12055351