Ketogenic diet administration to mice after a high-fat-diet regimen promotes weight loss, glycemic normalization and induces adaptations of ketogenic pathways in liver and kidney

Nasser, Souad; Solé, Thomas; Véga, Nathalie; Thomas, Thierry; Balcerczyk, Aneta; Strigini, Maura; Pirola, Luciano

doi:10.1016/j.molmet.2022.101578

Cited by 28 publications

(27 citation statements)

References 44 publications

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“…Consistent with previous findings in animals and humans [ 20 , 30 , 31 ], we also report a significant glucose-lowering effect of nutritional ketosis. Interestingly, the lower the initial BG concentration was, measured just prior to insulin injection, the larger was the magnitude of epinephrine counterregulatory response ( Figure 5 ).…”

Section: Discussionsupporting

confidence: 93%

Still Excited, but Less Aroused—The Effects of Nutritional Ketosis on Epinephrine Response and Hypothalamic Orexin Neuron Activation Following Recurrent Hypoglycemia in Diabetic Rats

Nedoboy

Farnham

2022

Metabolites

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Hypoglycemia-associated autonomic failure (HAAF) is a serious, life-threatening complication of intensive insulin therapy, particularly in people with type 1 diabetes. The ketogenic diet is reported to beneficially affect glycemic control in people with type 1 diabetes, however its effects on the neurohormonal counterregulatory response to recurrent hypoglycemia and HAAF development are understudied. In this study we used Sprague Dawley rats to establish a HAAF model under non-diabetic and streptozotocin (STZ)-induced diabetic conditions and determined how nutritional ketosis affected the neurohormonal counterregulation and the activity of energy-sensing orexin (OX) neurons. We found that antecedent hypoglycemia diminished the sympathoexcitatory epinephrine response to subsequent hypoglycemia in chow-fed non-diabetic rats, but this did not occur in STZ-diabetic animals. In all cases a ketogenic diet preserved the epinephrine response. Contrary to expectations, STZ-diabetic keto-fed rats showed reduced OX activity in the recurrent hypoglycemia group, which did not occur in any other group. It is possible that the reduced activation of OX neurons is an adaptation aimed at energy conservation accompanied by diminished arousal and exploratory behaviour. Our data suggests that while a ketogenic diet has beneficial effects on glycemia, and epinephrine response, the reduced activation of OX neurons could be detrimental and warrants further investigation.

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Section: Discussionsupporting

confidence: 93%

Still Excited, but Less Aroused—The Effects of Nutritional Ketosis on Epinephrine Response and Hypothalamic Orexin Neuron Activation Following Recurrent Hypoglycemia in Diabetic Rats

Nedoboy

Farnham

2022

Metabolites

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“…The same results were obtained with β-hydroxybutyrate in vitro . A ketogenic diet may improve liver lipid load by inducing the expression of genes involved in ketogenesis and ketolysis, such as HMGSC2, during which the Kbhb level changes significantly, but acetylation levels do not …”

Section: Introductionsupporting

confidence: 76%

“…124 A ketogenic diet may improve liver lipid load by inducing the expression of genes involved in ketogenesis and ketolysis, such as HMGSC2, during which the Kbhb level changes significantly, but acetylation levels do not. 125 In 2021, Huang et al systematically explored the substrates and regulatory enzymes of Kbhb. 126 As a member of acylations, Kbhb has the same writers, CBP/P300.…”

Section: Succinylationmentioning

confidence: 99%

Protein Post-Translational Modifications Based on Proteomics: A Potential Regulatory Role in Animal Science

Fan,

Kong,

Zhou

et al. 2024

J. Agric. Food Chem.

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Genomic studies in animal breeding have provided a wide range of references; however, it is important to note that genes and mRNA alone do not fully capture the complexity of living organisms. Protein post-translational modification, which involves covalent modifications regulated by genetic and environmental factors, serves as a fundamental epigenetic mechanism that modulates protein structure, activity, and function. In this review, we comprehensively summarize various phosphorylation and acylation modifications on metabolic enzymes relevant to energy metabolism in animals, including acetylation, succinylation, crotonylation, β-hydroxybutylation, acetoacetylation, and lactylation. It is worth noting that research on animal energy metabolism and modification regulation lags behind the demands for growth and development in animal breeding compared to human studies. Therefore, this review provides a novel research perspective by exploring unreported types of modifications in livestock based on relevant findings from human or animal models.

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“… 567 KbHb has the effect of improving obesity. 568 Oral β-hydroxybutyric acid has been reported to improve blood lipid status by increasing HDL levels and reducing LDL/HDL ratios in Wistar rats. 198 There is growing evidence that β-OHB is beneficial in vascular function and metabolism.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies

Geng

et al. 2023

Sig Transduct Target Ther

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The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. The most common form of NCD is metabolic diseases, which affect people of all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding of the pathobiology of metabolic diseases will generate novel targets for improved therapies across the common metabolic spectrum. Protein posttranslational modification (PTM) is an important term that refers to biochemical modification of specific amino acid residues in target proteins, which immensely increases the functional diversity of the proteome. The range of PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, and several novel PTMs. Here, we offer a comprehensive review of PTMs and their roles in common metabolic diseases and pathological consequences, including diabetes, obesity, fatty liver diseases, hyperlipidemia, and atherosclerosis. Building upon this framework, we afford a through description of proteins and pathways involved in metabolic diseases by focusing on PTM-based protein modifications, showcase the pharmaceutical intervention of PTMs in preclinical studies and clinical trials, and offer future perspectives. Fundamental research defining the mechanisms whereby PTMs of proteins regulate metabolic diseases will open new avenues for therapeutic intervention.

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Ketogenic diet administration to mice after a high-fat-diet regimen promotes weight loss, glycemic normalization and induces adaptations of ketogenic pathways in liver and kidney

Cited by 28 publications

References 44 publications

Still Excited, but Less Aroused—The Effects of Nutritional Ketosis on Epinephrine Response and Hypothalamic Orexin Neuron Activation Following Recurrent Hypoglycemia in Diabetic Rats

Still Excited, but Less Aroused—The Effects of Nutritional Ketosis on Epinephrine Response and Hypothalamic Orexin Neuron Activation Following Recurrent Hypoglycemia in Diabetic Rats

Protein Post-Translational Modifications Based on Proteomics: A Potential Regulatory Role in Animal Science

Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies

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