Location: Children's Nutrition Research CenterTitle: Metabolic inflexibility in youth with obesity: Is it a feature of obesity or distinctive of youth who are metabolically unhealthy?
|GEBARA, NOUR - University Of Pittsburgh Medical Center|
|KIM, JOON - Syracuse University|
|BACHA, FIDA - Children'S Nutrition Research Center (CNRC)|
|LEE, SOJUNG - Kyung Hee University|
|ARSLANIAN, SILVA - University Of Pittsburgh Medical Center|
Submitted to: Clinical Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2021
Publication Date: 12/1/2022
Citation: Gebara, N.Y., Kim, J.Y., Bacha, F., Lee, S., Arslanian, S. 2022. Metabolic inflexibility in youth with obesity: Is it a feature of obesity or distinctive of youth who are metabolically unhealthy? Clinical Obesity. 12(2). Article e12501. https://doi.org/10.1111/cob.12501.
Interpretive Summary: Metabolic inflexibility refers to decreased fat oxidation in fasting state and less increase in glucose oxidation and respiratory quotient (RQ) in insulin-stimulated states. Researchers in Texas and colleagues investigated whether metabolic flexibility is present in all children with obesity. They studied youth who were divided, based on vivo insulin sensitivity (IS) into 137 with metabolically unhealthy obesity (MUO) and 51 with metabolically healthy obesity (MHO). They demonstrated that metabolic inflexibility is not a feature of obesity per se rather distinctive of youth with metabolically unhealthy obesity, who also have worse insulin sensitivity at the muscle, liver and adipose tissue.
Technical Abstract: Individuals with obesity have metabolic inflexibility with diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) in insulin-stimulated states. However, it is unclear if metabolic inflexibility is a characteristic of obesity per se or is unique to youth who have metabolically unhealthy obesity (MUO) compared with metabolically healthy obesity (MHO). We investigated metabolic flexibility in youth with MUO, MHO and normal weight (NW) and compared their metabolic characteristics. Youth (n = 188) were divided, based on cut-off points for in vivo insulin sensitivity (IS) of adolescents with NW, into 137 with MUO and 51 with MHO. Fasting hepatic IS (HIS) from hepatic glucose production by [6,6-2H2]glucose, adipose tissue IS (ATIS) from whole-body lipolysis by [2H5]glycerol, RQ (indirect calorimetry) during fasting and a hyperinsulinemic (80 mU/m2/min)-euglycemic clamp were measured. Youth with MUO versus MHO had blunted deltaRQ (p = .035) and lower HIS and ATIS (both p < .0001), while deltaRQ, HIS and ATIS were not different between youth with MHO and NW. In a pair-matched sub-analyses of 30 MUO and 30 MHO the results were similar to the total cohort. Metabolic inflexibility, does not appear to be a feature of obesity per se rather distinctive of youth with MUO, who also have worse HIS and ATIS compared with youth with MHO.