A high-fat, ketogenic diet induces a unique metabolic state in mice

2007 ◽  
Vol 292 (6) ◽  
pp. E1724-E1739 ◽  
Author(s):  
Adam R. Kennedy ◽  
Pavlos Pissios ◽  
Hasan Otu ◽  
Bingzhong Xue ◽  
Kenji Asakura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Energy Expenditure ◽  
Ketogenic Diet ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
High Fat ◽  
Metabolic State ◽  
Ketogenic Diets ◽  
Low Carbohydrate

Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.

scholarly journals A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss

2009 ◽  
Vol 297 (5) ◽  
pp. E1197-E1204 ◽  
Author(s):  
Michael K. Badman ◽  
Adam R. Kennedy ◽  
Andrew C. Adams ◽  
Pavlos Pissios ◽  
Eleftheria Maratos-Flier
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Ketogenic Diet ◽  
Glucose Homeostasis ◽  
Energy Homeostasis ◽  
Caloric Intake ◽  
Normal Weight ◽  
Metabolic Effects ◽  
Fibroblast Growth Factor 21 ◽  
Low Carbohydrate

In mice of normal weight and with diet-induced obesity, a high-fat, low-carbohydrate ketogenic diet (KD) causes weight loss, reduced circulating glucose and lipids, and dramatic changes in hepatic gene expression. Many of the effects of KD are mediated by fibroblast growth factor 21 (FGF21). We tested the effects of KD feeding on ob/ ob mice to determine if metabolic effects would occur in obesity secondarily to leptin deficiency. We evaluated the effect of prolonged KD feeding on weight, energy homeostasis, circulating metabolites, glucose homeostasis, and gene expression. Subsequently, we evaluated the effects of leptin and fasting on FGF21 expression in ob/ ob mice. KD feeding of ob/ ob mice normalized fasting glycemia and substantially reduced insulin and lipid levels in the absence of weight loss. KD feeding was associated with significant increases in lipid oxidative genes and reduced expression of lipid synthetic genes, including stearoyl-coenzyme A desaturase 1, but no change in expression of inflammatory markers. In chow-fed ob/ ob mice, FGF21 mRNA was elevated 10-fold compared with wild-type animals, and no increase from this elevated baseline was seen with KD feeding. Administration of leptin to chow-fed ob/ ob mice led to a 24-fold induction of FGF21. Fasting also induced hepatic FGF21 in ob/ ob mice. Thus, KD feeding improved ob/ ob mouse glucose homeostasis without weight loss or altered caloric intake. These data demonstrate that manipulation of dietary macronutrient composition can lead to marked improvements in metabolic profile of leptin-deficient obese mice in the absence of weight loss.

Fat-Free Mass Changes During Ketogenic Diets and the Potential Role of Resistance Training

2016 ◽  
Vol 26 (1) ◽  
pp. 78-92 ◽  
Author(s):  
Grant M. Tinsley ◽  
Darryn S. Willoughby
Keyword(s):  
Weight Loss ◽  
Resistance Training ◽  
Ketogenic Diet ◽  
Potential Role ◽  
Mass Measurement ◽  
Fat Free Mass ◽  
Exercise Interventions ◽  
Ketogenic Diets ◽  
Low Carbohydrate

Low-carbohydrate and very-low-carbohydrate diets are often used as weight-loss strategies by exercising individuals and athletes. Very-low-carbohydrate diets can lead to a state of ketosis, in which the concentration of blood ketones (acetoacetate, 3-β-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and activity of ketogenic enzymes. A potential concern of these ketogenic diets, as with other weight-loss diets, is the potential loss of fat-free mass (e.g., skeletal muscle). On examination of the literature, the majority of studies report decreases in fat-free mass in individuals following a ketogenic diet. However, some confounding factors exist, such as the use of aggressive weight-loss diets and potential concerns with fat-free mass measurement. A limited number of studies have examined combining resistance training with ketogenic diets, and further research is needed to determine whether resistance training can effectively slow or stop the loss of fat-free mass typically seen in individuals following a ketogenic diet. Mechanisms underlying the effects of a ketogenic diet on fat-free mass and the results of implementing exercise interventions in combination with this diet should also be examined.

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

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.

scholarly journals A Low-Protein High-Fat Diet Leads to Loss of Body Weight and White Adipose Tissue Weight via Enhancing Energy Expenditure in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 301
Author(s):  
Yifeng Rang ◽  
Sihui Ma ◽  
Jiao Yang ◽  
Huan Liu ◽  
Katsuhiko Suzuki ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Plasma Biomarkers ◽  
Low Protein

Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.

scholarly journals Popular Diets: Ketogenic Diet

EDIS ◽  
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

scholarly journals Non-hematopoietic IL-4Rα expression contributes to fructose-driven obesity and metabolic sequelae

2021 ◽  
Author(s):  
Michelle S. M. A. Damen ◽  
Traci E. Stankiewicz ◽  
Se-Hyung Park ◽  
Robert N. Helsley ◽  
Calvin C. Chan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Energy Expenditure ◽  
Signaling Pathway ◽  
Acid Oxidation ◽  
High Fat ◽  
Inflammatory Gene Expression ◽  
Hepatocellular Damage ◽  
Deficient Mice

Abstract Objective The risks of excess sugar intake in addition to high-fat diet consumption on immunopathogenesis of obesity-associated metabolic diseases are poorly defined. Interleukin-4 (IL-4) and IL-13 signaling via IL-4Rα regulates adipose tissue lipolysis, insulin sensitivity, and liver fibrosis in obesity. However, the contribution of IL-4Rα to sugar rich diet-driven obesity and metabolic sequelae remains unknown. Methods WT, IL-4Rα-deficient (IL-4Rα−/−) and STAT6-deficient mice (STAT6−/−) male mice were fed low-fat chow, high fat (HF) or HF plus high carbohydrate (HC/fructose) diet (HF + HC). Analysis included quantification of: (i) body weight, adiposity, energy expenditure, fructose metabolism, fatty acid oxidation/synthesis, glucose dysmetabolism and hepatocellular damage; (ii) the contribution of the hematopoietic or non-hematopoietic IL-4Rα expression; and (iii) the relevance of IL-4Rα downstream canonical STAT6 signaling pathway in this setting. Results We show that IL-4Rα regulated HF + HC diet-driven weight gain, whole body adiposity, adipose tissue inflammatory gene expression, energy expenditure, locomotor activity, glucose metabolism, hepatic steatosis, hepatic inflammatory gene expression and hepatocellular damage. These effects were potentially, and in part, dependent on non-hematopoietic IL-4Rα expression but were independent of direct STAT6 activation. Mechanistically, hepatic ketohexokinase-A and C expression was dependent on IL-4Rα, as it was reduced in IL-4Rα-deficient mice. KHK activity was also affected by HF + HC dietary challenge. Further, reduced expression/activity of KHK in IL-4Rα mice had a significant effect on fatty acid oxidation and fatty acid synthesis pathways. Conclusion Our findings highlight potential contribution of non-hematopoietic IL-4Rα activation of a non-canonical signaling pathway that regulates the HF + HC diet-driven induction of obesity and severity of obesity-associated sequelae.

scholarly journals Severe ketoacidosis in a non-diabetic lactating woman on a ketogenic diet

2020 ◽  
Vol 20 (2) ◽  
pp. 145-146
Author(s):  
John Alexander ◽  
Dinesh Nagi
Keyword(s):  
Ketogenic Diet ◽  
Breast Feeding ◽  
Carbohydrate Content ◽  
Efficacy And Safety ◽  
High Fat ◽  
Term Efficacy ◽  
Ketogenic Diets ◽  
Low Carbohydrate

Ketogenic diets are high fat, moderate protein, low carbohydrate diets with carbohydrate content usually less than 50 g/day. They are a novel intervention in the management of obesity and there is emerging evidence that they are very effective. Evidence regarding the long-term efficacy and safety of this rather new and popular intervention is still emerging and there is a lack of data on the effect of this diet in specific populations such as breast feeding women. We describe a case of severe ketoacidosis in a non-diabetic breast feeding woman who was successfully treated with conservative measures. This case highlights the need by medical and dietetic professionals for extra caution in initiating special dietary measures in susceptible physiological states.

scholarly journals A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain

2010 ◽  
Vol 299 (5) ◽  
pp. E808-E815 ◽  
Author(s):  
François R. Jornayvaz ◽  
Michael J. Jurczak ◽  
Hui-Young Lee ◽  
Andreas L. Birkenfeld ◽  
David W. Frederick ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Lipid Metabolism ◽  
Weight Gain ◽  
Food Intake ◽  
Energy Expenditure ◽  
Hepatic Insulin Resistance ◽  
High Fat ◽  
Ketogenic Diets

Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more effective in promoting weight loss than conventional caloric restriction, whereas their effect on hepatic glucose and lipid metabolism and the mechanisms by which they may promote weight loss remain controversial. The aim of this study was to explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid metabolism, energy expenditure, and food intake. Using hyperinsulinemic-euglycemic clamps, we studied insulin action in mice fed a KD or regular chow (RC). Body composition was assessed by 1H magnetic resonance spectroscopy. Despite being 15% lighter ( P < 0.001) than RC-fed mice because of a 17% increase in energy expenditure ( P < 0.001), KD-fed mice manifested severe hepatic insulin resistance, as reflected by decreased suppression (0% vs. 100% in RC-fed mice, P < 0.01) of endogenous glucose production during the clamp. Hepatic insulin resistance could be attributed to a 350% increase in hepatic diacylglycerol content ( P < 0.001), resulting in increased activation of PKCε ( P < 0.05) and decreased insulin receptor substrate-2 tyrosine phosphorylation ( P < 0.01). Food intake was 56% ( P < 0.001) lower in KD-fed mice, despite similar caloric intake, and could partly be attributed to a more than threefold increase ( P < 0.05) in plasma N-acylphosphatidylethanolamine concentrations. In conclusion, despite preventing weight gain in mice, KD induces hepatic insulin resistance secondary to increased hepatic diacylglycerol content. Given the key role of nonalcoholic fatty liver disease in the development of type 2 diabetes and the widespread use of KD for the treatment of obesity, these results may have potentially important clinical implications.

scholarly journals A Low-Carbohydrate Ketogenic Diet and Treadmill Training Enhanced Fatty Acid Oxidation Capacity but Did Not Enhance Maximal Exercise Capacity in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 611
Author(s):  
Sihui Ma ◽  
Jiao Yang ◽  
Takaki Tominaga ◽  
Chunhong Liu ◽  
Katsuhiko Suzuki
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Exercise Capacity ◽  
Ketogenic Diet ◽  
Maximal Exercise ◽  
Treadmill Running ◽  
Acid Oxidation ◽  
Oxidation Capacity ◽  
Low Carbohydrate ◽  
Maximal Exercise Capacity

The low-carbohydrate ketogenic diet (LCKD) is a dietary approach characterized by the intake of high amounts of fat, a balanced amount of protein, and low carbohydrates, which is insufficient for metabolic demands. Previous studies have shown that an LCKD alone may contribute to fatty acid oxidation capacity, along with endurance. In the present study, we combined a 10-week LCKD with an 8-week forced treadmill running program to determine whether training in conjunction with LCKD enhanced fatty acid oxidation capacity, as well as whether the maximal exercise capacity would be affected by an LCKD or training in a mice model. We found that the lipid pool and fatty acid oxidation capacity were both enhanced following the 10-week LCKD. Further, key fatty acid oxidation related genes were upregulated. In contrast, the 8-week training regimen had no effect on fatty acid and ketone body oxidation. Key genes involved in carbohydrate utilization were downregulated in the LCKD groups. However, the improved fatty acid oxidation capacity did not translate into an enhanced maximal exercise capacity. In summary, while favoring the fatty acid oxidation system, an LCKD, alone or combined with training, had no beneficial effects in our intensive exercise-evaluation model. Therefore, an LCKD may be promising to improve endurance in low- to moderate-intensity exercise, and may not be an optimal choice for those partaking in high-intensity exercise.

Sign in / Sign up

Export Citation Format

Share Document