Gut microbiota regulates hepatic ketogenesis and lipid accumulation in ketogenic diet-induced hyperketonemia by disrupting bile acid metabolism

Gut Microbes, Год журнала: 2025, Номер 17(1)

Опубликована: Апрель 23, 2025

The ketogenic diet (KD) induces prolonged hyperketonemia, characterized by elevated circulating level of β-hydroxybutyrate. However, the KD can negatively affect host metabolic health altering gut microbial community. Despite this, regulatory effect microbiota on hepatic ketogenesis and triacylglycerol (TAG) accumulation during a remains poorly understood. Here, we hypothesized that commensal bacterium regulates lipid metabolism in association with KD-induced hyperketonemia. disrupts remodeling following antibiotic-induced depletion. capacity for severity TAG liver closely correlated changes composition up-regulation farnesoid X receptor (FXR), peroxisome proliferator-activated alpha (PPARα), diacylglycerol O-acyltransferase 2 (DGAT2), which were modulated bile acid through gut-liver axis. Clostridium perfringens type A is particularly implicated exacerbating steatosis disrupting secondary metabolism. increased conversion deoxycholic to 12-ketolithocholic represents critical pathway C. colonization. These findings illuminate adverse effects adaptation highlight role ketonic states.

Язык: Английский

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Effects of a Ketogenic Diet on Body Composition in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial

Nutrients, Год журнала: 2024, Номер 16(13), С. 2030 - 2030

Опубликована: Июнь 26, 2024

This study investigates the effects of a ketogenic low-carbohydrate high-fat (LCHF) diet on body composition in healthy, young, normal-weight women. With increasing interest diets for their various health benefits, this research aims to understand impact composition, focusing women who are often underrepresented such studies. Conducting randomized controlled feeding trial with crossover design, compares LCHF Swedish National Food Agency (NFA)-recommended control over four weeks. Seventeen adhered strictly provided diets, ketosis confirmed through blood β-hydroxybutyrate concentrations. Dual-energy X-ray absorptiometry (DXA) was utilized precise measurements. To avoid bias, all statistical analyses were performed blind. The findings reveal that led significant reduction both lean mass (−1.45 kg 95% CI: [−1.90;−1.00]; p < 0.001) and fat (−0.66 [−1.00;−0.32]; compared diet, despite similar energy intake physical activity levels. concludes while is effective weight loss, it disproportionately reduces mass, suggesting need concurrent strength training mitigate muscle loss following diet.

Язык: Английский

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Intermittent fasting, fatty acid metabolism reprogramming, and neuroimmuno microenvironment: mechanisms and application prospects

Frontiers in Nutrition, Год журнала: 2024, Номер 11

Опубликована: Окт. 24, 2024

Intermittent fasting (IF) has demonstrated extensive health benefits through the regulation of fatty acid metabolism and modulation neuroimmune microenvironment, primarily via activation key signaling pathways such as AMP-activated protein kinase (AMPK) sirtuin 1 (SIRT1). IF not only facilitates oxidation improves metabolic health, but also enhances mitochondrial function, mitigates oxidative stress, promotes autophagy, inhibits apoptosis ferroptosis. These mechanisms contribute to its substantial preventive therapeutic potential in various conditions, including neurodegenerative disorders Alzheimer’s Parkinson’s diseases, autoimmune neurotraumatic conditions. While supportive evidence been obtained from animal models preliminary clinical studies, further large-scale, long-term randomized controlled trials are imperative establish safety evaluate efficacy comprehensively.

Язык: Английский

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The Catabolic - Anabolic Cycling Hormesis Model of Health and Resilience

Ageing Research Reviews, Год журнала: 2024, Номер unknown, С. 102588 - 102588

Опубликована: Ноя. 1, 2024

Язык: Английский

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Nutraceuticals Modulating Mitophagy May Combat the Mitochondrial Dysfunction and Redox Stress in Several Cardiac Disorders

Опубликована: Апрель 16, 2024

It has been proposed that procedures which up-regulate mitochondrial biogenesis and autophagy by replacing damaged mitochondria with healthy ones, may prevent the development of several heart diseases. A member serine threonine kinases, AMPK, could play essential roles in and/or mitophagy. AMPK is widely distributed various cells, might diverse regulatory different tissues organs. In fact, changes kinase function due to alteration activity have linked pathologies including cardiac disorders. can regulate via PGC1α signaling also improve oxidative metabolism through inhibition mTOR pathway, modulate autophagy/mitophagy ULK1 TGF-β signaling. Therefore, modulation pathway be considered as a therapeutic tactic for As kinases are amongst most controllable proteins, general, design small molecules targeting an eye-catching avenue function. Some analyses molecular biology underlying mitophagy suggests nutraceuticals drugs specific modulator well physical exercise dietary restriction useful against particular, some nutraceutical regimens encouraging potential controlling

Язык: Английский

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Exogenous and Endogenous Molecules Potentially Proficient to Modulate Mitophagy in Cardiac Disorders

Kinases and Phosphatases, Год журнала: 2024, Номер 2(2), С. 166 - 178

Опубликована: Май 23, 2024

It has been proposed that procedures which upregulate mitochondrial biogenesis and autophagy by replacing damaged mitochondria with healthy ones may prevent the development of several heart diseases. A member serine threonine kinases, adenosine monophosphate-activated protein kinase (AMPK), could play essential roles in and/or mitophagy. AMPK is widely distributed various cells, might diverse regulatory different tissues organs. In fact, changes function due to alteration activity have linked pathologies including cardiac disorders. can regulate via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) signaling also improve oxidative metabolism through inhibition mechanistic/mammalian target rapamycin (mTOR) pathway, modulate autophagy/mitophagy activating 1 (ULK1) transforming growth factor beta (TGF-β) signaling. Therefore, modulation pathway probably be thought as a therapeutic tactic for As kinases are amongst most controllable proteins, general, design small molecules targeting an eye-catching avenue function. Some analyses molecular biology underlying mitophagy suggest nutraceuticals drugs specific modulator well physical exercise dietary restriction useful against These observations virtually limited preclinical studies. Come think these, however, it speculated some nutraceutical regimens positive potential managing

Язык: Английский

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Anti-Tumor Effect and Mechanism Study of Caloric Restriction, Achieved by Time-Restricted Feeding, in Mice

Cancer Control, Год журнала: 2024, Номер 31

Опубликована: Янв. 1, 2024

Objective To evaluate the therapeutic effects and explore mechanisms behind caloric restriction achieved through time-restricted feeding (CR) in inhibiting mouse tumors, providing a theoretical basis data support for future CR diet-assisted anticancer treatment protocols. Methods C57BL/6 BALB/c mice were divided into four cell line groups. Each group was further split normal diet (ND) The ND groups had free access to water diet, while but only fed from 9 a.m. 11 a.m., fasting remaining 22 h. Food intake recorded daily starting on day 1 of experiment. Tumor models established assessed every 2 days. Blood biochemical indicators, serum pyruvic acid levels, cytokine expression measured. Results inhibited tumor growth mice. Colorimetric assays ELISAs showed reduction levels key upstream downstream rate-limiting enzymes sera Routine blood biochemistry tests suggested minor these parameters. Western blotting revealed that suppressed mTOR AKT protein tissues. ELISA various mTOR-related signaling pathways downregulated. Immunohistochemistry staining indicated reduced P53, P-AKT, EGFR, IGF-1 TUNEL confirmed promoted apoptosis. Conclusion by suppressing its related gene pathways, reducing glycolysis, accelerating

Язык: Английский

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The impact of mild episodic ketosis on microglia and hippocampal long‐term depression in 5xFAD mice

FASEB BioAdvances, Год журнала: 2024, Номер 6(12), С. 581 - 596

Опубликована: Окт. 23, 2024

Abstract Ketotherapeutics is a potential metabolic intervention for mitigating dementias; however, its mechanisms and optimal methods of application are not well understood. Our previous in vitro study showed that β‐hydroxybutyrate (BHB), major ketone body, reverses pathological features amyloid‐β oligomer (AβO)‐activated microglia. Here we tested the vivo effects BHB on microglia synaptic plasticity 5xFAD Alzheimer's disease (AD) mouse model. A short 1‐week regimen daily intraperitoneal injection (250 mg/kg), which induced brief mild episodic ketosis, was sufficient to mitigate pro‐inflammatory activation reduce brain deposition by enhancing phagocytosis. Remarkably, it mitigated deficits hippocampal long‐term depression but potentiation, this effect linked suppression NLRP3 inflammasome‐generated IL‐1β. As ketogenic diets known poor compliance, our opens possibility alternative approaches such as short‐term injections or dietary esters less restrictive, potentially safer, easier compliance.

Язык: Английский

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Effects of a 12 Week Ketogenic Diet Intervention on Obese and Overweight Females with Glucose and Lipid Metabolism Disturbance

Nutrients, Год журнала: 2024, Номер 16(23), С. 4218 - 4218

Опубликована: Дек. 6, 2024

We evaluated the effects of a 12-week hypocaloric ketogenic diet (KD) on glucose and lipid metabolism, as well body mass, in overweight, obese, healthy-weight females. One hundred adult females completed study, including 64 obese (97.99 ± 11.48 kg), 23 overweight (75.50 5.12 11 with normal mass (65.93 3.40 kg). All participants followed KD consisting less than 30 g carbohydrates, approximately 60 protein, 140 fat per day (80% unsaturated 20% saturated fat).

Язык: Английский

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