A study examined the effects of a 5-day high-fat diet on skeletal muscle metabolism in young healthy males. The high-fat diet disrupted the normal increase seen in postprandial glucose and fatty acid oxidation in skeletal muscle in response to a high-fat meal. Metabolic flexibility, the ability of skeletal muscle to switch between fat and carbohydrate oxidation, was also blunted after the high-fat diet. However, whole-body insulin sensitivity and intestinal permeability were unaffected by the short-term high-fat diet. The findings demonstrate that even short changes in dietary fat intake can impair skeletal muscle metabolic adaptation independent of energy balance or insulin sensitivity.

1. Short-term high fat diet impairs postprandial metabolic flexibility in skeletal muscle.
Suzanne Bowser, Ryan McMillan, Nabil Boutagy, Michael Tarpey, Kris Osterberg, Madlyn Frisard, Andrew Nielson, Brenda Davy, Kevin Davy, and Matthew Hulver.
Department of Human Nutrition, Foods, and Exercise
Metabolic Phenotyping Core
Virginia Tech, Blacksburg, VA
Abstract
Background: The ability of skeletal muscle to adapt and
respond to various nutrient states is important to
maintaining healthy metabolic function; disruptions in
these processes are known to associate with obesity,
metabolic syndrome and diabetes. The purpose of this
study was to determine the effects of an acute, 5-day,
isocaloric high fat diet (HFD) on skeletal muscle
postprandial substrate metabolism in healthy, non-
obese, male humans.
Methods: Thirteen participants (age 22.2 ± 1. years,
BMI 22.3 ± 2.8) were fed a control diet that was
isocaloric to their habitual diet (kcal, 2768 ± 65.6,
30.9% fat, 9.4% of kcal saturated fat) for two weeks,
followed by 5 days of isocaloric HFD (53.8% fat, 24.5%
of kcal saturated fat, HFD). To assess the effects of HFD
on skeletal muscle metabolic adaptability, subjects
underwent a high fat meal challenge (kcal ~30% of daily
energy intake, 64% fat) before and after HFD. Muscle
biopsies were obtained immediately, prior to (after
overnight fast) and 4 hours following the meal. Skeletal
muscle substrate metabolism was assessed by
measuring the oxidation of [U-14C]-glucose and [1-14C-
palmitic acid, and metabolic flexibility was assessed by
measuring [1-14C]-pyruvate oxidation +/- palmitic acid.
Insulin sensitivity was assessed prior to and following
HFD via intravenous glucose tolerance test. Intestinal
permeability was assessed in the same manner via
sugar probe test.
Results: Postprandial glucose oxidation in skeletal
muscle increased (+96.9% ± 36.3) before HFD but not
after (-24.3% ± 4.5, p=0.003). Postprandial fatty acid
oxidation followed a similar pattern increasing 106.3% ±
36.6 and was blunted to 15.6% ± 20.8 after the HFD
(p=0.0412). Skeletal muscle metabolic flexibility was
significantly blunted following HFD (-24.7%). Insulin
sensitivity and intestinal permeability were not affected
by HFD.
Conclusions: These findings demonstrate that skeletal
muscle metabolic adaptation is compromised in young,
healthy males following only 5 days of an isocaloric high
fat diet. These findings suggest that even short-term
changes in dietary fat consumption have profound
effects on skeletal muscle substrate metabolism
independent of positive energy balance and whole-body
insulin sensitivity.
Glucose Oxidation
%Changerelativeto
Control
FUNDING
American Diabetes Association (MWH)
CONTACT
Suzanne Bowser (suz@vt.edu)
Conclusions
Skeletal muscle metabolic adaptation is altered in
young healthy males following a 5 day HFD.
- Short term changes in dietary fat consumption
have profound effects on skeletal muscle substrate
metabolism and metabolic flexibility
- Effects are independent of:
- Positive energy balance
- Whole-body insulin sensitivity
Diet CompositionParticipant Characteristics Insulin Sensitivity
Metabolic Flexibility
Intestinal Permeability
Insulin sensitivity was
assessed by
intravenous glucose
tolerance test before
and after HFD.
Insulin sensitivity was
not affected.
Intestinal permeability was assessed using sugar probe
test. No effect was shown after 5 days of HFD.
Postprandial glucose oxidation in skeletal muscle increased
(+96.9% ± 36.3) before HFD but not after (-24.3% ± 4.5,
p=0.003). Five days of isocaloric high fat feeding disrupted
postprandial glucose oxidation.
Diet
Condition
Energy
(kcal/day) Protein (%) CHO (%) Fat (%) SFA (%kcal)
Pre HFD
(control)
2768.4 ± 65.6 15.2 53.9 30.9 9.4
High Fat 2734.8 ± 73.4 15.3 30.9 53.8 24.5
HF Meal
Challenge
768
kcal/meal
25.7g/meal 44.2g/meal 53.9g/meal 29.9
(25.5g/meal)
Skeletal muscle to increased FAO after a meal by
106.3% ± 36.6, however, after 5 days of HFD, this
effect was blunted to15.6% ± 20.8 (p=0.0412).
Metabolic flexibility was assessed by measuring [1-
14C]-pyruvate oxidation+/- palmitic acid. In response to
the meal, skeletal muscle metabolic flexibility was
significantly blunted following HFD (-24.7%).
Fatty Acid Oxidation
2wk lead-in diet
(isocaloric)
Muscle Biopsies
HF Meal Challenge
5day HFD
(isocaloric)
Muscle Biopsies
HF Meal Challenge
Glucose Oxidation
Pre HFD Post HFD
0
2
4
6
8
10
Pre Meal Challenge
Post Meal Challenge
nmol/mg/hr
Glucose Oxidation
response to meal challenge
Pre HFD Post HFD
-50
0
50
100
150
PercentChange
inresponsetomealchallenge
* p = 0.003 compared to Pre HFD
*
Measure p value
Diet effect 0.450
Meal effect 0.863
Diet x meal interaction 0.011
Measure p value
Diet effect 0.506
Meal effect 0.200
Diet x meal interaction 0.002
Measure p value
Diet effect 0.649
Meal effect 0.002
Diet x meal interaction 0.032
Metabolic Flexibility
Pre HFD Post HFD
0.0
0.5
1.0
1.5
2.0
2.5
Pre Meal Challenge
Post Meal Challenge
Ratioof[1-14C]-pyruvateoxidationto
[1-14C]-pyruvateoxidation+FFA
Metabolic Flexibility
response to meal challenge
Pre HFD Post HFD
0
10
20
30
40
50
PercentChange
inresponsetomealchallenge
* p = 0.014 compared to Pre HFD
*
Fatty Acid Oxidation
response to meal challenge
Pre HFD Post HFD
0
50
100
150
PercentChange
inresponsetomealchallenge
*
* p = 0.041 compared to Pre HFD
Fatty Acid Oxidation
Pre HFD Post HFD
0
5
10
15
Pre Meal Challenge
Post Meal Challenge
nmol/mg/hr
Pre HFD Post HFD
0
5
10
15
[(mU/L)/min]
Variable (n=13) Pre HFD Post HFD
Age (yrs) 22.2 ± 0.4 --
Height (m) 1.77 ± 0.02 --
BMI (kg/m2) 23.1 ± 0.9 23.0 ± 0.8
Body Mass (kg) 72.09 ± 3.2 71.98 ± 2.9
Body Fat Mass (kg) 16.57 ± 2.1 16.28 ± 2.0
Body Fat (%) 22.03 ± 1.7 21.44 ± 1.7
Lean Mass (kg) 54.15 ± 1.7 54.51 ± 1.9