scholarly journals Cardiac metabolic modulation upon low‐carbohydrate low‐protein ketogenic diet in diabetic rats studied in vivo using hyperpolarized13C pyruvate, butyrate and acetoacetate probes

2019 ◽  
Vol 21 (4) ◽  
pp. 949-960 ◽  
Author(s):  
Desiree Abdurrachim ◽  
Xing Qi Teo ◽  
Chern Chiuh Woo ◽  
Sing Yee Ong ◽  
Nurul Farhana Salleh ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Diabetic Rats ◽  
Low Protein ◽  
Metabolic Modulation ◽  
Low Carbohydrate

scholarly journals Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet

2011 ◽  
Vol 300 (6) ◽  
pp. G956-G967 ◽  
Author(s):  
Joel R. Garbow ◽  
Jason M. Doherty ◽  
Rebecca C. Schugar ◽  
Sarah Travers ◽  
Mary L. Weber ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Western Diet ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Chow Diet ◽  
High Fat ◽  
Low Protein ◽  
Low Carbohydrate ◽  
Term Administration

Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.

scholarly journals The efficacy of a ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma

2021 ◽  
Author(s):  
Rodrigo Javier ◽  
Wenxia Wang ◽  
Michael Drumm ◽  
Kathleen McCortney ◽  
Jann N. Sarkaria ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Sleeping Beauty ◽  
Standard Diet ◽  
Wild Type ◽  
Preclinical Models ◽  
Isocitrate Dehydrogenase 1 ◽  
Low Carbohydrate ◽  
Cellular Biochemistry

ABSTRACTInfiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1) or, less commonly, IDH2 (together called “IDHmut”). These mutations alter cellular biochemistry, and IDHmut gliomas are generally less aggressive than IDH wild-type (IDHwt) gliomas. Some preclinical studies and clinical trials have suggested that a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, not all studies have shown promising results, and to date, no study has addressed whether IDHmut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of KD in preclinical models of IDHwt versus IDHmut gliomas. In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDHwt or IDHmut glioma cells. Likewise, a cycling KD, wherein mice alternated between KD and a standard diet (SD), had no effect on the in vivo growth of patient-derived IDHwt or IDHmut gliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDHmut glioma. These data suggest that neither IDHwt nor IDHmut gliomas are particularly responsive to KD.

scholarly journals The ketogenic diet is not effective in preclinical models of IDH1 wild-type and IDH1 mutant glioma

2020 ◽  
Author(s):  
Rodrigo Javier ◽  
Craig Horbinski
Keyword(s):  
Clinical Trials ◽  
Ketogenic Diet ◽  
Sleeping Beauty ◽  
Wild Type ◽  
Preclinical Models ◽  
Isocitrate Dehydrogenase 1 ◽  
Low Carbohydrate ◽  
Cellular Biochemistry

ABSTRACTInfiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut). This mutation disrupts cellular biochemistry, and IDH1mut gliomas are generally less aggressive than IDH1 wild-type (IDH1wt) gliomas. Some preclinical studies and clinical trials have suggested that a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, not all studies have shown promising results, and to date, no study has addressed whether IDH1mut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of KD in preclinical models of IDH1wt versus IDH1mut gliomas. In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDH1wt or IDH1mut glioma cells. Likewise, KD had no effect on the in vivo growth of these patient-derived gliomas. Furthermore, mice engrafted with Sleeping-Beauty transposase-engineered IDH1wt and IDH1mut glioma showed no difference in survival while on KD. These data suggest that IDH1mut gliomas are not more responsive to KD, and that clinical trials further exploring KD in this subset of glioma patients may not be warranted.

scholarly journals Ketogenic Diet for Cancer: Critical Assessment and Research Recommendations

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3562
Author(s):  
Jordin Lane ◽  
Nashira I. Brown ◽  
Shanquela Williams ◽  
Eric P. Plaisance ◽  
Kevin R. Fontaine
Keyword(s):  
Clinical Trials ◽  
Ketogenic Diet ◽  
The United States ◽  
Carbohydrate Content ◽  
Cancer Development ◽  
Antitumor Effects ◽  
Low Protein ◽  
Low Carbohydrate ◽  
Diet And Lifestyle ◽  
Research Recommendations

Despite remarkable improvements in screening, diagnosis, and targeted therapies, cancer remains the second leading cause of death in the United States. It is increasingly clear that diet and lifestyle practices play a substantial role in cancer development and progression. As such, various dietary compositions have been proposed for reducing cancer risk and as potential adjuvant therapies. In this article, we critically assess the preclinical and human trials on the effects of the ketogenic diet (KD, i.e., high-fat, moderate-to-low protein, and very-low carbohydrate content) for cancer-related outcomes. The mechanisms underlying the hypothesized effects of KD, most notably the Warburg Effect, suggest that restricting carbohydrate content may impede cancer development and progression via several pathways (e.g., tumor metabolism, gene expression). Overall, although preclinical studies suggest that KD has antitumor effects, prolongs survival, and prevents cancer development, human clinical trials are equivocal. Because of the lack of high-quality clinical trials, the effects of KD on cancer and as an adjunctive therapy are essentially unknown. We propose a set of research recommendations for clinical studies examining the effects of KD on cancer development and progression.

scholarly journals Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e74806 ◽  
Author(s):  
Rebecca C. Schugar ◽  
Xiaojing Huang ◽  
Ashley R. Moll ◽  
Elizabeth M. Brunt ◽  
Peter A. Crawford
Keyword(s):  
Fatty Liver ◽  
Ketogenic Diet ◽  
Choline Deficiency ◽  
Low Protein ◽  
Low Carbohydrate

Effect of dietary protein on in vivo insulin action and liver glycogen repletion

1989 ◽  
Vol 257 (2) ◽  
pp. E212-E219 ◽  
Author(s):  
L. Rossetti ◽  
D. L. Rothman ◽  
R. A. DeFronzo ◽  
G. I. Shulman
Keyword(s):  
Insulin Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Dietary Manipulation ◽  
Low Protein ◽  
Hepatic Glucose ◽  
Low Carbohydrate ◽  
Glycogen Repletion

To investigate the influence of dietary manipulation on in vivo glucose metabolism, we pair fed normal rats for 10 days with one of three diets: 1) high protein-low carbohydrate (Hi-PN) (n = 20); 2) intermediate protein (I-PN) (n = 11); and 3) low protein-high carbohydrate (Lo-PN) (n = 18). Fasting glucose, postmeal plasma glucose, and insulin concentrations were as follows: 118 +/- 2 mg/dl, 138 +/- 2 mg/dl, and 4.0 +/- 0.2 ng/ml in Hi-PN; 111 +/- 3 mg/dl, 147 +/- 3 mg/dl, and 5.1 +/- 0.3 ng/ml in I-PN; 102 +/- 2 mg/dl, 162 +/- 2 mg/dl, and 6.0 +/- 0.2 ng/ml in Lo-PN, respectively. Basic hepatic glucose production (HGP) was 6.6 +/- 0.2 in Hi-PN, 6.1 +/- 0.2 in I-PN, and 5.6 +/- 0.1 mg.kg-1.min-1 in Lo-PN. Insulin sensitivity was assessed with the euglycemic clamp using two insulin infusion rates: 2 and 4 mU.kg-1.min-1. The rate of glucose disappearance was 14.8 +/- 0.4 and 25.3 +/- 0.7 in Hi-PN, 15.3 +/- 0.4 and 26.9 +/- 0.5 in I-PN, and 16.1 +/- 0.6 and 31.5 +/- 0.5 mg.kg-1.min-1 in Lo-PN, respectively. HGP was suppressed by 86 in the 2- and by 90% in the 4-mU insulin clamp in the Lo-PN, whereas HGP was suppressed by 45 and by 79% in the two steps in the Hi-PN group.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document