Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats

Ogura, Yuji; Kakehashi, Chiaki; Yoshihara, Toshinori; Kurosaka, Mitsutoshi; Kakigi, Ryo; Higashida, Kazuhiko; Fujiwara, Satoshi; Akema, Tatsuo; Funabashi, Toshiya

doi:10.1371/journal.pone.0241382

Cited by 8 publications

(10 citation statements)

References 60 publications

(93 reference statements)

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“…Additionally, KDs may strengthen bioenergetic signaling that upregulates mitochondrial fat oxidation and endogenous antioxidant defense and downregulates inflammation [ 111 ]. In sedentary rats, a KD improved oxidative capacity and aerobic energy metabolism in muscle, without compromising muscle performance [ 117 ].…”

Section: Cellular Mechanisms Of Kds In Pdac and Cachexiamentioning

confidence: 99%

Ketogenic Diets in Pancreatic Cancer and Associated Cachexia: Cellular Mechanisms and Clinical Perspectives

Cortez

Mackenzie

2021

Nutrients

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and extremely therapy-resistant cancer. It is estimated that up to 80% of PDAC patients present with cachexia, a multifactorial disorder characterized by the involuntary and ongoing wasting of skeletal muscle that affects therapeutic response and survival. During the last decade, there has been an increased interest in exploring dietary interventions to complement the treatment of PDAC and associated cachexia. Ketogenic diets (KDs) have gained attention for their anti-tumor potential. Characterized by a very low carbohydrate, moderate protein, and high fat composition, this diet mimics the metabolic changes that occur in fasting. Numerous studies report that a KD reduces tumor growth and can act as an adjuvant therapy in various cancers, including pancreatic cancer. However, research on the effect and mechanisms of action of KDs on PDAC-associated cachexia is limited. In this narrative review, we summarize the evidence of the impact of KDs in PDAC treatment and cachexia mitigation. Furthermore, we discuss key cellular mechanisms that explain KDs’ potential anti-tumor and anti-cachexia effects, focusing primarily on reprogramming of cell metabolism, epigenome, and the gut microbiome. Finally, we provide a perspective on future research needed to advance KDs into clinical use.

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Section: Cellular Mechanisms Of Kds In Pdac and Cachexiamentioning

confidence: 99%

Ketogenic Diets in Pancreatic Cancer and Associated Cachexia: Cellular Mechanisms and Clinical Perspectives

Cortez

Mackenzie

2021

Nutrients

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“…Several β-hydroxybutyric acid isoforms are potential targets for intervention in sarcopenic obesity. Supplementary of Ketogenic Diet Is Good for Aging-Related Sarcopenic Obesity DOI: http://dx.doi.org/10.5772/intechopen.96028 acetoacetic acid and β-hydroxybutyric acid prevents muscle atrophy due to nutrient deprivation [35]. A ketogenic diet regulates metabolism in skeletal muscle and may inhibit oxidative metabolism during aging.…”

Section: Ketogenic Diet Is Good For Aging-related Sarcopenic Obesitymentioning

confidence: 99%

“…Earlier models concentrated on the effect of the ketogenic diet on sarcopenic obesity. The effects on the ketogenic diet and satiety, weight loss, and nitrogen balance are discussed as well as influences on electrolytes and the sympathetic system [38]. Hormonal changes of the ketogenic diet regimens and the impact on mood and subjective acceptance are compared.…”

Section: Ketogenic Diet Is Good For Aging-related Sarcopenic Obesitymentioning

confidence: 99%

Ketogenic Diet Is Good for Aging-Related Sarcopenic Obesity

Suchkov¹,

Salmi²,

Bai³

et al. 2021

Role of Obesity in Human Health and Disease

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Sarcopenic obesity is a skeletal muscle weight loss disease. It has happened at an elderly age. A ketogenic diet is a low-carbohydrate (5%), moderate protein (15%), and a higher-fat diet (80%) can help sarcopenic obese patients burn their fat more effectively. It has many benefits for muscle and fat weight loss. A ketogenic diet can be especially useful for losing excess body fat without hunger and for improving type 2 diabetes. That is because of only a few carbohydrates in the diet, the liver converts fat into fatty acids and ketones. Ketone bodies can replace higher ATP energy. This diet forces the human body to burn fat. This is a good way to lose fat weight without restriction.

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“…Indeed, Fukazawa et al showed that a KD increased the protein content of the ketolytic enzyme 3-oxoacid CoA transferase (OXCT) in the epitrochlearis (Epit) muscle [ 11 ], whereas Shimizu et al reported a significant attenuation of OXCT gene expression in the gastrocnemius muscle [ 5 ]. Moreover, there is evidence that the KD increases mitochondrial mass in the red gastrocnemius muscle [ 7 ], which was contrasted by reports that the KD did not alter PGC-1α levels in the extensor digitorum longus (EDL) [ 12 ] or soleus (Sol) muscles [ 6 ]. Taken together, these data point to an apparent gap in the literature where KD-induced metabolic adaptations in substrate preference in muscles of varying oxidative and glycolytic capacities are yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Sucrose-Enriched and Carbohydrate-Free High-Fat Diets Distinctly Affect Substrate Metabolism in Oxidative and Glycolytic Muscles of Rats

Da Eira,

Jani,

Stefanovic

et al. 2024

Nutrients

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Skeletal muscle substrate preference for fuel is largely influenced by dietary macronutrient availability. The abundance of dietary carbohydrates promotes the utilization of glucose as a substrate for energy production, whereas an abundant dietary fat supply elevates rates of fatty acid (FA) oxidation. The objective of this study was to determine whether an obesogenic, high-fat, sucrose-enriched (HFS) diet or a carbohydrate-free ketogenic diet (KD) exert distinct effects on fat, glucose, and ketone metabolism in oxidative and glycolytic skeletal muscles. Male Wistar rats were fed either a HFS diet or a KD for 16 weeks. Subsequently, the soleus (Sol), extensor digitorum longus (EDL), and epitrochlearis (Epit) muscles were extracted to measure palmitate oxidation, insulin-stimulated glucose metabolism, and markers of mitochondrial biogenesis, ketolytic capacity, and cataplerotic and anaplerotic machinery. Sol, EDL, and Epit muscles from KD-fed rats preserved their ability to elevate glycogen synthesis and lactate production in response to insulin, whereas all muscles from rats fed with the HFS diet displayed blunted responses to insulin. The maintenance of metabolic flexibility with the KD was accompanied by muscle-fiber-type-specific adaptive responses. This was characterized by the Sol muscle in KD-fed rats enhancing mitochondrial biogenesis and ketolytic capacity without elevating its rates of FA oxidation in comparison with that in HFS feeding. Conversely, in the Epit muscle, rates of FA oxidation were increased, whereas the ketolytic capacity was markedly reduced by the KD in comparison with that by HFS feeding. In the EDL muscle, the KD also increased rates of FA oxidation, although it did so without altering its ketolytic capacity when compared to HFS feeding. In conclusion, even though obesogenic and ketogenic diets have elevated contents of fat and alter whole-body substrate partitioning, these two dietary interventions are associated with opposite outcomes with respect to skeletal muscle metabolic flexibility.

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Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats

Cited by 8 publications

References 60 publications

Ketogenic Diets in Pancreatic Cancer and Associated Cachexia: Cellular Mechanisms and Clinical Perspectives

Ketogenic Diets in Pancreatic Cancer and Associated Cachexia: Cellular Mechanisms and Clinical Perspectives

Ketogenic Diet Is Good for Aging-Related Sarcopenic Obesity

Sucrose-Enriched and Carbohydrate-Free High-Fat Diets Distinctly Affect Substrate Metabolism in Oxidative and Glycolytic Muscles of Rats

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