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A ketogenic diet enhances aerobic exercise adaptation and promotes muscle mitochondrial remodeling in hyperglycemic mice.

Research square
January 29, 2025
Pattarawan Pattamaprapanont et al. (9 authors)
Journal ArticlePreprintAnimal Study
Study Details

Study Goal

The researchers aimed to determine whether a ketogenic diet could restore the impaired aerobic exercise adaptation caused by chronic hyperglycemia in mice.

Results Summary

The study found that a ketogenic diet normalized blood glucose and restored aerobic exercise adaptation in hyperglycemic mice, improving VO2peak, skeletal muscle remodeling, capillary density, and mitochondrial function. The diet also independently enhanced fatty acid oxidation.

Population

Hyperglycemic mice induced by streptozotocin (STZ).

Effective Dosage

Not specified

Duration

Not specified

Interactions

None mentioned

Extracted Claims (10)
InterventionDirectionEndpointPopulationDosageImpactClaim #
a low-carbohydrate/high-fat 'ketogenic' diet
decrease
blood glucose
a mouse model of hyperglycemia
-
reducing
#1
a ketogenic diet
decrease
blood glucose
STZ-KETO mice
-
rapidly normalized
#2
aerobic exercise training
no change
VO2peak
STZ-CHOW mice
-
improvements in VO2peak were blunted
#3
aerobic exercise training
increase
VO2peak
STZ-KETO mice
-
exercise response was restored
#4
a ketogenic diet
increase
aerobic remodeling of skeletal muscle
STZ-KETO mice
-
enhanced aerobic remodeling of skeletal muscle
#5
a ketogenic diet
increase
skeletal muscle fiber-type
STZ-KETO mice
-
more oxidative fiber-type
#6
a ketogenic diet
increase
capillary density
STZ-KETO mice
-
increased capillary density
#7
a ketogenic diet
increase
circulating angiogenic markers
STZ-KETO mice
-
restoration of circulating angiogenic markers
#8
a ketogenic diet
increase
muscle mitochondrial remodeling and mitochondrial dynamics
STZ-KETO mice
-
induced exercise-independent effects on muscle mitochondrial remodeling and mitochondrial dynamics
#9
a ketogenic diet
increase
fatty acid oxidation
STZ-KETO mice
-
significantly increasing
#10
Abstract

VO2peak is a key health benefit of aerobic exercise; however, chronic hyperglycemia is associated with persistently low VO2peak due to an impaired adaptive response to training. Here, we tested whether reducing blood glucose with a low-carbohydrate/high-fat "ketogenic" diet could restore aerobic exercise adaptation in a mouse model of hyperglycemia. Hyperglycemia was induced by streptozotocin (STZ) and mice were stratified to standard chow (STZ-CHOW), or a ketogenic diet (STZ-KETO), which rapidly normalized blood glucose. After aerobic exercise training, improvements in VO2peak were blunted in STZ-CHOW, but exercise response was restored in STZ-KETO. Improved VO2peak in STZ-KETO was associated with enhanced aerobic remodeling of skeletal muscle, including a more oxidative fiber-type and increased capillary density, along with restoration of circulating angiogenic markers. Moreover, KETO induced exercise-independent effects on muscle mitochondrial remodeling and mitochondrial dynamics, significantly increasing fatty acid oxidation. Our results identify a ketogenic diet as a potential therapy to improve aerobic exercise response in the growing population with hyperglycemia due to diabetes and other metabolic conditions.

Study Links
Quality Scores
SafetyNot Assessed
Efficacy85/10
Quality75/10
Research Impact Scores
APT Score0.05
Weight Score1.25
Normalized Score0.69
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