Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 May 2;25(5):1027-1036.
doi: 10.1016/j.cmet.2017.04.015.

Metabolic Flexibility in Health and Disease

Bret H Goodpaster  1 , Lauren M Sparks  2
Affiliations
Review

Metabolic Flexibility in Health and Disease

Bret H Goodpaster et al. Cell Metab. .

Abstract

Metabolic flexibility is the ability to respond or adapt to conditional changes in metabolic demand. This broad concept has been propagated to explain insulin resistance and mechanisms governing fuel selection between glucose and fatty acids, highlighting the metabolic inflexibility of obesity and type 2 diabetes. In parallel, contemporary exercise physiology research has helped to identify potential mechanisms underlying altered fuel metabolism in obesity and diabetes. Advances in "omics" technologies have further stimulated additional basic and clinical-translational research to further interrogate mechanisms for improved metabolic flexibility in skeletal muscle and adipose tissue with the goal of preventing and treating metabolic disease.

Keywords: adipose tissue; exercise; insulin resistance; metabolic flexibility; obesity; skeletal muscle; type 2 diabetes.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Acute lipid oversupply during hyperinsulinemia reveals metabolic flexibility in trained compared to untrained subjects
During a hyperinsulinemic-euglycemic “glucose” clamp without (light bars) or with (dark bars) co-infusion of intralipid, trained subjects decrease glucose oxidation (green bars), increase fatty acid oxidation (yellow bars) and preserve muscle glycogen storage (red bars) relative to untrained subjects, who exhibit metabolic inflexibility. In other words, untrained subjects do not effectively decrease glucose oxidation or increase fatty acid oxidation, and they have diminished glycogen storage in the face of lipid overload. Data were obtained from (Dube et al., 2014).
Figure 2
Figure 2. Adipose tissue insulin responsiveness is critical for metabolic flexibility of other organs and is blunted in diabetes
(a) Free fatty acids (FFAs) during a during a hyperinsulinemic-euglycemic clamp with a primed-continuous insulin infusion of 80 mU/m2/min for 3–4 hours are related to reduced metabolic flexibility (delta RQ) in a population of 56 healthy young men subdivided into quartiles of metabolic flexibility. (b) People with type 2 diabetes (T2D; n=18) have significantly higher levels of FFAs during an hyperinsulinemic-euglycemic clamp with a primed-continuous insulin infusion of 100 mU/m2/min for 3–4 hours compared with age- and BMI-matched healthy people (ND; n=6) and highly active people (Active; n=8). ANOVA was used to test for differences across quartiles of metabolic flexibility (delta RQ), with post hoc testing by mean equality contrast between different groups using the Tukey–Kramer HSD; alpha = 0.05. Type I error rate was set a priori at p < 0.05. Data are shown as means ± SEM. Levels which do not share the same letter are significantly different. FFAs were measured by high-performance liquid chromatography (HPLC) for (a) and by enzyme assay for (b).
Figure 3
Figure 3. Transcapillary flux of FFAs is reduced with obesity
The release of free fatty acids (FFAs) and the extraction of triglycerides from plasma (nmol/100g/min) in abdominal subcutaneous white adipose tissue (WAT) is significantly lower in the WAT of abdominally obese men (red line) compared with lean men (blue line) (both time x group, p < 0.001) across consumption of three mixed meals over the course of 24 hours. Meal consumption is indicated by a dashed line.
Figure 4
Figure 4. Respiratory quotient (RQ) kinetic during 24 hours in a metabolic chamber
Lines represent individual responses for a type I diabetes mellitus patient (DMT1, red line) and a healthy volunteer (blue line). Arrows indicate different features of metabolic flexibility (exercise, response to a meal and sleeping) as assessed in whole room respiratory chamber.
Figure 5
Figure 5. Summary of fuel metabolism changes within skeletal muscle and adipose tissue during periods of sleeping, fasting, feeding, rest and exercise
Skeletal muscle switches from higher rates of fatty acid oxidation during sleeping/post-absorptive conditions to greater oxidation and storage of glucose after feeding, and reduced fatty acid oxidation. Adipose tissue shifts from higher rates of lipolysis to suppression of lipolysis and fat storage during the fasting to feeding transition. From rest to exercise, skeletal muscle increases rates of both fatty acid and glucose oxidation to support higher energy demands, while lipolysis in adipose tissue is drastically enhanced.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aas V, Bakke SS, Feng YZ, Kase ET, Jensen J, Bajpeyi S, Thoresen GH, Rustan AC. Are cultured human myotubes far from home? Cell Tissue Res. 2013;354:671–682. - PubMed
    1. Acheson KJ, Ravussin E, Wahren J, Jequier E. Thermic effect of glucose in man. Obligatory and facultative thermogenesis. Journal of Clinical Investigation. 1984;74:1572–1580. - PMC - PubMed
    1. Amati F, Dube JJ, Alvarez-Carnero E, Edreira MM, Chomentowski P, Coen PM, Switzer GE, Bickel PE, Stefanovic-Racic M, Toledo FG, et al. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes. 2011;60:2588–2597. - PMC - PubMed
    1. Andres R, Cadar G, Zierler K. The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state. Journal of Clinical Investigation. 1956;35:671–682. - PMC - PubMed
    1. Arduini A, Zammit VA. A tennis lesson: sharp practice in the science behind the Sharapova case. Postgrad Med J. 2016;92:429–430. - PMC - PubMed