Funding agencies: This research was funded by ADA-07–12 (MWH) and RO1DK078765 (MWH).
Brief Cutting Edge Report
Early skeletal muscle adaptations to short-term high-fat diet in humans before changes in insulin sensitivity
Version of Record online: 27 MAR 2015
© 2015 The Obesity Society
Volume 23, Issue 4, pages 720–724, April 2015
How to Cite
Anderson, A. S., Haynie, K. R., McMillan, R. P., Osterberg, K. L., Boutagy, N. E., Frisard, M. I., Davy, B. M., Davy, K. P. and Hulver, M. W. (2015), Early skeletal muscle adaptations to short-term high-fat diet in humans before changes in insulin sensitivity. Obesity, 23: 720–724. doi: 10.1002/oby.21031
Disclosure: The authors declared no conflict of interest.
Author contributions: AA analyzed data, interpreted data, and wrote the manuscript. KH recruited subjects, conceived the study design, and carried out experiments. RM conceived and carried out experiments. KO contributed to the study design and planned/provided all meals to the subjects. NB and BD contributed to the study design and edited the document. MF, KD, and MH conceived the study design and experiments and contributed to editing of the document. All authors gave final approval of the submitted and published versions.
- Issue online: 27 MAR 2015
- Version of Record online: 27 MAR 2015
- Manuscript Accepted: 13 DEC 2014
- Manuscript Revised: 17 NOV 2014
- Manuscript Received: 30 JUN 2014
- ADA-07–12 (MWH). Grant Number: RO1DK078765
The purpose of this investigation was to understand the metabolic adaptations to a short-term (5 days), isocaloric, high-fat diet (HFD) in healthy, young males.
Two studies were undertaken with 12 subjects. Study 1 investigated the effect of the HFD on skeletal muscle substrate metabolism and insulin sensitivity. Study 2 assessed the metabolic and transcriptional responses in skeletal muscle to the transition from a fasted to fed state using a high-fat meal challenge before and after 5 days of the HFD.
Study 1 showed no effect of a HFD on skeletal muscle metabolism or insulin sensitivity in fasting samples. Study 2 showed that a HFD elicits significant increases in fasting serum endotoxin and disrupts the normal postprandial excursions of serum endotoxin, as well as metabolic and transcriptional responses in skeletal muscle. These effects after 5 days of the HFD were accompanied by an altered fasting and postprandial response in the ratio of phosphorylated- to total-p38 protein. These changes all occurred in the absence of alterations in insulin sensitivity.
Our findings provide evidence for early biological adaptations to high-fat feeding that proceed and possibly lead to insulin resistance.