Fgf21 Impairs Adipocyte Insulin Sensitivity in Mice Fed a Low-Carbohydrate, High-Fat Ketogenic Diet

The ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis and weight loss. It is known to induce ketosis but is not an established cause of clinically significant ketoacidosis. Lactation ketoacidosis is well established in bovine literature but remains a rare phenomenon in humans. Here we present a life-threatening case of severe ketoacidosis in a nondiabetic lactating mother on a strict ketogenic diet. We review the available case reports of lactation ketoacidosis in humans and the mechanisms thereof. Although ketogenic diet has been shown to be safe in nonpregnant individuals, the safety of this diet in lactating mothers is not known. Health professionals and mothers should be made aware of the potential risk associated with a strict ketogenic diet when combined with lactation. Prompt diagnosis and immediate treatment cannot be overemphasized. To our knowledge, this is the first reported case of life-threatening lactation ketoacidosis associated with ketogenic diet while consuming an adequate number of calories per day.

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Long-Term Ketogenic Diet Induces Metabolic Acidosis, Anemia, and Oxidative Stress in Healthy Wistar Rats

Journal of Nutrition and Metabolism ◽

10.1155/2020/3642035 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Aryadi Arsyad ◽

Irfan Idris ◽

Andi A. Rasyid ◽

Rezky A. Usman ◽

Kiki R. Faradillah ◽

...

Keyword(s):

Superoxide Dismutase ◽

Metabolic Acidosis ◽

Ketogenic Diet ◽

Wistar Rats ◽

Blood Gas ◽

High Fat ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

Low Carbohydrate

Background. Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and cancer. Objective. This study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, hematological profiles, organ functions, and superoxide dismutase level in a rat model. Materials and Methods. Fifteen male Wistar rats were divided into control (n = 8) and ketogenic (n = 7) groups. Controls received standard diet contained 52.20% of carbohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either standard or high-fat-low-carbohydrate pellets. The experiment was carried out for 60 days before the blood samples were taken and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels. Results. The rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood ketones (p<0.05). The average blood pH was 7.36 ± 0.02 and base excess was −5.57 ± 2.39 mOsm/L, which were significantly lower than controls (p<0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels. No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. Conclusion. Long-term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of consuming high-fat-low-carbohydrate diet.

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00539.2010 ◽

2011 ◽

Vol 300 (6) ◽

pp. G956-G967 ◽

Cited By ~ 84

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.

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A low-carbohydrate high-fat ketogenic diet program implemented by an interdisciplinary primary care team improves markers of cardiometabolic health in adults with type 2 diabetes: A retrospective secondary analysis

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2021.09.001 ◽

2021 ◽

Author(s):

Helena Neudorf ◽

Michael Mindrum ◽

Christa Mindrum ◽

Cody Durrer ◽

Jonathan P. Little

Keyword(s):

Type 2 Diabetes ◽

Primary Care ◽

Ketogenic Diet ◽

Secondary Analysis ◽

Care Team ◽

Primary Care Team ◽

Cardiometabolic Health ◽

High Fat ◽

Low Carbohydrate

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Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00809.2015 ◽

2016 ◽

Vol 311 (1) ◽

pp. H1-H10 ◽

Cited By ~ 6

Author(s):

Jian Liu ◽

Peipei Wang ◽

Samuel L. Douglas ◽

Joshua M. Tate ◽

Simon Sham ◽

...

Keyword(s):

Insulin Sensitivity ◽

Cardiac Function ◽

Ischemia Reperfusion ◽

Substrate Oxidation ◽

Left Ventricular ◽

High Fat ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

Low Carbohydrate ◽

Myocardial Substrate

High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels.

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Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00208.2013 ◽

2013 ◽

Vol 305 (9) ◽

pp. E1059-E1070 ◽

Cited By ~ 41

Author(s):

Maximilian Bielohuby ◽

Stephanie Sisley ◽

Darleen Sandoval ◽

Nadja Herbach ◽

Ayse Zengin ◽

...

Keyword(s):

Weight Loss ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Glucose Intolerance ◽

Fasting Glucose ◽

Male Rats ◽

High Fat ◽

Insulin Metabolism ◽

Low Carbohydrate

Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein “Atkins-style” LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.

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The Chemistry of the Ketogenic Diet: Updates and Opportunities in Organic Synthesis

International Journal of Molecular Sciences ◽

10.3390/ijms22105230 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5230

Author(s):

Michael Scott Williams ◽

Edward Turos

Keyword(s):

Weight Loss ◽

Chemical Synthesis ◽

Organic Synthesis ◽

Ketogenic Diet ◽

Health Benefits ◽

The Body ◽

High Fat ◽

Strict Adherence ◽

Chemical Basis ◽

Low Carbohydrate

The high-fat, low-carbohydrate (ketogenic) diet has grown in popularity in the last decade as a weight loss tool. Research into the diet’s effects on the body have revealed a variety of other health benefits. The use of exogenous ketone supplements to confer the benefits of the diet without strict adherence to it represents an exciting new area of focus. Synthetic ketogenic compounds are of particular interest that has received very little emphasis and is an untapped area of focus for chemical synthesis. In this review, we summarize the chemical basis for ketogenicity and opportunities for further advancement of the field.

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Popular Diets: Ketogenic Diet

EDIS ◽

10.32473/edis-fs403-2020 ◽

2020 ◽

Vol 2020 (5) ◽

Author(s):

Kelsey Gemmill ◽

Daniela Rivero-Mendoza ◽

Wendy J. Dahl

Keyword(s):

Social Media ◽

Weight Loss ◽

Ketogenic Diet ◽

Human Nutrition ◽

Food Science ◽

High Fat ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

The Past ◽

Low Carbohydrate

The ketogenic diet is a high-fat, very low carbohydrate diet. The first documented use of the ketogenic diet was in 1921 to treat epilepsy in children. In the past few years, the ketogenic diet has resurged in popularity as a potential means for weight loss. The ketogenic diet has become popular due to celebrity endorsement and social media influences. This new 4-page publication of the UF/IFAS Food Science and Human Nutrition Department explains the concepts behind this diet, explores the available menu, and examines whether this diet is safe and effective. Written by Kelsey Gemmill, Daniela Rivero-Mendoza, and Wendy Dahl.https://edis.ifas.ufl.edu/fs403

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