bims-kimdis 2023-07-30 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2023‒07‒30
fifteen papers selected by
Matías Javier Monsalves Álvarez

β-hydroxybutyrate: A crucial therapeutic target for diverse liver diseases.
Ketogenic diet and β-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway.
Efficacy, safety and tolerability of very low-calorie ketogenic diet in obese women with fibromyalgia: a pilot interventional study.
The Computational Acid-Base Chemistry of Hepatic Ketoacidosis.
The Effects of Ketogenic Diet on Insulin Sensitivity and Weight Loss, Which Came First: The Chicken or the Egg?
Mitochondrial dysfunction: roles in skeletal muscle atrophy.
Weight, insulin resistance, blood lipids, and diet quality changes associated with ketogenic and ultra low-fat dietary patterns: a secondary analysis of the DIETFITS randomized clinical trial.
(R,R)-BD-AcAc2 Mitigates Chronic Colitis in Rats: A Promising Multi-Pronged Approach Modulating Inflammasome Activity, Autophagy, and Pyroptosis.
Exercise, mitochondrial dysfunction and inflammasomes in skeletal muscle.
1,3-Butanediol Administration Increases β-Hydroxybutyrate Plasma Levels and Affects Redox Homeostasis, Endoplasmic Reticulum Stress, and Adipokine Production in Rat Gonadal Adipose Tissue.
Hepatic ketogenesis regulates lipid homeostasis via ACSL1-mediated fatty acid partitioning.
2:1 ketogenic diet and low-glycemic-index diet for the treatment of chronic and episodic migraine: a single-center real-life retrospective study.
Research progress of NLRP3 inflammasome and its inhibitors with aging diseases.
Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects.
The Potential of Fasting-Mimicking Diet as a Preventive and Curative Strategy for Alzheimer's Disease.

Biomed Pharmacother. 2023 Jul 22. pii: S0753-3322(23)00982-4. [Epub ahead of print]165 115191

β-hydroxybutyrate: A crucial therapeutic target for diverse liver diseases.

Ke Li, Wen-Hong Wang, Jia-Bin Wu, Wei-Hua Xiao.

  β-hydroxybutyrate (β-HB), the most abundant ketone body, is produced primarily in the liver and acts as a substitute energy fuel to provide energy to extrahepatic tissues in the event of hypoglycemia or glycogen depletion. We now have an improved understanding of β-HB as a signal molecule and epigenetic regulatory factor as a result of intensive research over the last ten years. Because β-HB regulates various physiological and pathological processes, it may have a potential role in the treatment of metabolic diseases. The liver is the most significant metabolic organ, and the part that β-HB plays in liver disorders is receiving increasing attention. In this review, we summarize the therapeutic effects of β-HB on liver diseases and its underlying mechanisms of action. Moreover, we explore the prospects of exogenous supplements and endogenous ketosis including fasting, caloric restriction (CR), ketogenic diet (KD), and exercise as adjuvant nutritional therapies to protect the liver from damage and provide insights and strategies for exploring the treatment of various liver diseases.

Keywords:  Ketone body; Liver diseases; Mechanism; Therapeutic; β-hydroxybutyrate

DOI:  https://doi.org/10.1016/j.biopha.2023.115191
Eur J Pharmacol. 2023 Jul 20. pii: S0014-2999(23)00445-4. [Epub ahead of print]955 175933

Ketogenic diet and β-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway.

Chuman Lin, Shengnan Wang, Jiaxin Xie, Juan Zhu, Jiawei Xu, Kewei Liu, Jiancong Chen, Mingjia Yu, Hengren Zhong, Kaibin Huang, Suyue Pan.

  Ketogenic diet (KD) is a classical nonpharmacological therapy that has recently been shown to benefit cerebral ischemia, but the mechanism remains unclear. This study investigated the neuroprotective effects of KD pretreatment and β-hydroxybutyrate (BHB, bioactive product of KD) post-treatment in a mouse model of temporary middle cerebral artery occlusion (tMCAO). Neurological function, infarct volume, as well as inflammatory reactions are evaluated 24 h after ischemia. Results showed that both KD pretreatment or BHB post-treatment improved the Bederson score and Grip test score, reduced infarct volume and the extravasation of IgG, suppressed the over-activation of microglia, and modulated the expression of cytokines. Mechanically, we found that both KD pretreatment or BHB post-treatment significantly stimulated the expression of interleukin-1 receptor-associated kinase M (IRAKM) and then inhibited the nuclear translocation of NF-κB. IRAKM deletion (Irakm-/-) exacerbated tMCAO-induced neurovascular injuries, and aggravated neuroinflammatory response. Moreover, KD pretreatment or BHB post-treatment lost their neuroprotection in the tMCAO-treated Irakm-/- mice. Our results support that KD pretreatment and BHB post-treatment alleviate ischemic brain injury in mice, possibly via an IRAKM-dependent way.

Keywords:  IRAKM; Ischemic brain injury; Ketogenic diet; Proinflammatory cytokines; β-Hydroxybutyrate

DOI:  https://doi.org/10.1016/j.ejphar.2023.175933
Front Nutr. 2023 ;10 1219321

Efficacy, safety and tolerability of very low-calorie ketogenic diet in obese women with fibromyalgia: a pilot interventional study.

Jacopo Ciaffi, Lucia Lisi, Anna Mari, Luana Mancarella, Veronica Brusi, Federica Pignatti, Susanna Ricci, Giorgia Vitali, Nicola Stefanelli, Elisa Assirelli, Simona Neri, Susanna Naldi, Cesare Faldini, Francesco Ursini.

  Introduction: Obesity can worsen fibromyalgia (FM) and very low-calorie ketogenic diet (VLCKD) is a potential therapeutic option for diseases that share clinical and pathophysiological features with FM. In this pilot interventional study, we investigated the effects of VLCKD in obese women with FM.Methods: Female patients with FM and a body mass index (BMI) ≥ 30 kg/m2 were eligible for VLCKD. The ketogenic phase (T0 to T8) was followed by progressive reintroduction of carbohydrates (T8 to T20). Changes in BMI, Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), EuroQol 5D (EQ-5D) and 36-item Short Form Health Survey (SF-36) were evaluated. A change of 14% in FIQ was considered clinically relevant. The longitudinal association between BMI and patient-reported outcomes (PROs) was assessed using generalized estimating equations.
Results: Twenty women were enrolled. Two discontinued the intervention. The mean age of the 18 patients who reached T20 was 51.3 years and mean BMI was 37.2 kg/m2. All patients lost weight during the first period of VLCKD and this achievement was maintained at T20. Mean BMI decreased from 37.2 kg/m2 at T0 to 34.8 kg/m2 at T4, 33.5 kg/m2 at T8 and 32.1 kg/m2 at T20 (p < 0.001). A significant reduction of mean FIQ from 61.7 at T0 to 37.0 at T4 and to 38.7 at T8 (p < 0.001) was observed and it was maintained at T20 with a mean FIQ of 39.1 (p = 0.002). Similar results were obtained for HADS, EQ-5D and SF-36. Analysing each participant, the reduction of FIQ was clinically meaningful in 16 patients (89%) at T4, in 13 (72%) at T8 and in 14 (78%) at T20. No significant association was observed between change in BMI and improvement of the PROs over time. Adverse effects were mild and transient. No major safety concerns emerged.
Conclusion: These are the first data on the efficacy of VLCKD in FM. All patients achieved improvement in different domains of the disease, which was maintained also after carbohydrate reintroduction. Our results suggest that ketosis might exert beneficial effects in FM beyond the rapid weight loss.
Clinical trial registration: This trial is registered on ClinicalTrials.gov, number NCT05848544.

Keywords:  fibromyalgia; ketogenic diet; ketone bodies; obesity; pain

DOI:  https://doi.org/10.3389/fnut.2023.1219321
Metabolites. 2023 Jun 28. pii: 803. [Epub ahead of print]13(7):

The Computational Acid-Base Chemistry of Hepatic Ketoacidosis.

Samuel L Torrens, Robert A Robergs, Steven C Curry, Marek Nalos.

  Opposing evidence exists for the source of the hydrogen ions (H+) during ketoacidosis. Organic and computational chemistry using dissociation constants and alpha equations for all pertinent ionizable metabolites were used to (1) document the atomic changes in the chemical reactions of ketogenesis and ketolysis and (2) identify the sources and quantify added fractional (~) H+ exchange (~H+e). All computations were performed for pH conditions spanning from 6.0 to 7.6. Summation of the ~H+e for given pH conditions for all substrates and products of each reaction of ketogenesis and ketolysis resulted in net reaction and pathway ~H+e coefficients, where negative revealed ~H+ release and positive revealed ~H+ uptake. Results revealed that for the liver (pH = 7.0), the net ~H+e for the reactions of ketogenesis ending in each of acetoacetate (AcAc), β-hydroxybutyrate (β-HB), and acetone were -0.9990, 0.0026, and 0.0000, respectively. During ketogenesis, ~H+ release was only evident for HMG CoA production, which is caused by hydrolysis and not ~H+ dissociation. Nevertheless, there is a net ~H+ release during ketogenesis, though this diminishes with greater proportionality of acetone production. For reactions of ketolysis in muscle (pH = 7.1) and brain (pH = 7.2), net ~H+ coefficients for β-HB and AcAc oxidation were -0.9649 and 0.0363 (muscle), and -0.9719 and 0.0291 (brain), respectively. The larger ~H+ release values for β-HB oxidation result from covalent ~H+ release during the oxidation-reduction. For combined ketogenesis and ketolysis, which would be the metabolic condition in vivo, the net ~H+ coefficient depends once again on the proportionality of the final ketone body product. For ketone body production in the liver, transference to blood, and oxidation in the brain and muscle for a ratio of 0.6:0.2:0.2 for β-HB:AcAc:acetone, the net ~H+e coefficients for liver ketogenesis, blood transfer, brain ketolysis, and net total (ketosis) equate to -0.1983, -0.0003, -0.2872, and -0.4858, respectively. The traditional theory of ketone bodies being metabolic acids causing systemic acidosis is incorrect. Summation of ketogenesis and ketolysis yield H+ coefficients that differ depending on the proportionality of ketone body production, though, in general, there is a small net H+ release during ketosis. Products formed during ketogenesis (HMG-CoA, acetoacetate, β-hydroxybutyrate) are created as negatively charged bases, not acids, and the final ketone body, acetone, does not have pH-dependent ionizable groups. Proton release or uptake during ketogenesis and ketolysis are predominantly caused by covalent modification, not acid dissociation/association. Ketosis (ketogenesis and ketolysis) results in a net fractional H+ release. The extent of this release is dependent on the final proportionality between acetoacetate, β-hydroxybutyrate, and acetone.

Keywords:  acid–base balance; biochemistry; ketoacidosis; ketones; metabolism

DOI:  https://doi.org/10.3390/metabo13070803
Nutrients. 2023 Jul 12. pii: 3120. [Epub ahead of print]15(14):

The Effects of Ketogenic Diet on Insulin Sensitivity and Weight Loss, Which Came First: The Chicken or the Egg?

Antonio Paoli, Antonino Bianco, Tatiana Moro, Joao Felipe Mota, Christianne F Coelho-Ravagnani.

  The ketogenic diet (KD) is, nowadays, considered an interesting nutritional approach for weight loss and improvement in insulin resistance. Nevertheless, most of the studies available in the literature do not allow a clear distinction between its effects on insulin sensitivity per se, and the effects of weight loss induced by KDs on insulin sensitivity. In this review, we discuss the scientific evidence on the direct and weight loss mediated effects of KDs on glycemic status in humans, describing the KD's biochemical background and the underlying mechanisms.

Keywords:  body weight; insulin resistance; insulin sensitivity; ketogenic diet; very low carbohydrate diet; weight loss

DOI:  https://doi.org/10.3390/nu15143120
J Transl Med. 2023 07 26. 21(1): 503

Mitochondrial dysfunction: roles in skeletal muscle atrophy.

Xin Chen, Yanan Ji, Ruiqi Liu, Xucheng Zhu, Kexin Wang, Xiaoming Yang, Boya Liu, Zihui Gao, Yan Huang, Yuntian Shen, Hua Liu, Hualin Sun.

  Mitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a series of pathophysiological changes. Mitochondrial dysfunction can lead to skeletal muscle atrophy, and its molecular mechanism leading to skeletal muscle atrophy is complex. Understanding the pathogenesis of mitochondrial dysfunction is useful for the prevention and treatment of skeletal muscle atrophy, and finding drugs and methods to target and modulate mitochondrial function are urgent tasks in the prevention and treatment of skeletal muscle atrophy. In this review, we first discussed the roles of normal mitochondria in skeletal muscle. Importantly, we described the effect of mitochondrial dysfunction on skeletal muscle atrophy and the molecular mechanisms involved. Furthermore, the regulatory roles of different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 and NF-κB pathways, etc.) and the roles of mitochondrial factors were investigated in mitochondrial dysfunction. Next, we analyzed the manifestations of mitochondrial dysfunction in muscle atrophy caused by different diseases. Finally, we summarized the preventive and therapeutic effects of targeted regulation of mitochondrial function on skeletal muscle atrophy, including drug therapy, exercise and diet, gene therapy, stem cell therapy and physical therapy. This review is of great significance for the holistic understanding of the important role of mitochondria in skeletal muscle, which is helpful for researchers to further understanding the molecular regulatory mechanism of skeletal muscle atrophy, and has an important inspiring role for the development of therapeutic strategies for muscle atrophy targeting mitochondria in the future.

Keywords:  Antioxidants; Mitochondrial dysfunction; Muscle atrophy; Therapy

DOI:  https://doi.org/10.1186/s12967-023-04369-z
Front Nutr. 2023 ;10 1220020

Weight, insulin resistance, blood lipids, and diet quality changes associated with ketogenic and ultra low-fat dietary patterns: a secondary analysis of the DIETFITS randomized clinical trial.

Lucia Aronica, Matthew J Landry, Joseph Rigdon, Christopher D Gardner.

  Background: The DIETFITS trial reported no significant difference in 12-month weight loss between a healthy low-fat and healthy low-carbohydrate diet. Participants were instructed to restrict fat or carbohydrates to levels consistent with a ketogenic or ultra low-fat diet for 2 months and to subsequently increase intakes until they achieved a comfortable maintenance level.Objective: To compare 3- and 12-month changes in body weight and cardiometabolic risk factors between a subsample of participants who reported 3-month fat or carbohydrates intakes consistent with either a ketogenic-like diet (KLD) or ultra low-fat diet (ULF).
Design: 3-month and 12-month weight and risk factor outcomes were compared between KLD (n = 18) and ULF (n = 21) sub-groups of DIETFITS participants (selected from n = 609, healthy overweight/obese, aged 18-50 years).
Results: Less than 10% of DIETFITS participants met KLD or ULF criteria at 3-months. Both groups achieved similar weight loss and insulin resistance improvements at 3-months and maintained them at 12- months. Significant differences at 3-months included a transient ~12% increase in LDL cholesterol (LDL-C) for KLD with a concomitant greater reduction in log(TG/HDL), a measure of LDL-C's atherogenic potential. The latter was maintained at 12-months, despite substantial diet recidivism for both groups, whereas LDL-C levels were similar for ULF at baseline and 12-months. KLD participants achieved and maintained the greatest reductions in added sugars and refined grains at 3- months and 12-months, whereas ULF participants reported a 50% increase in refined grains intake from baseline to 12-months.
Conclusion: Among the ~10% of study participants that achieved the most extreme restriction of dietary fat vs. carbohydrate after 3 months, weight loss and improvement in insulin sensitivity were substantial and similar between groups. At 12 months, after considerable dietary recidivism, the few significant differences in diet quality and blood lipid parameters tended to favor KLD over ULF.

Keywords:  insulin resistance; ketogenic diet; low carbohydrate; low fat; refined grains; triglycerides/HDL ratio; ultra low-fat diet; weight loss

DOI:  https://doi.org/10.3389/fnut.2023.1220020
Pharmaceuticals (Basel). 2023 Jul 03. pii: 953. [Epub ahead of print]16(7):

(R,R)-BD-AcAc2 Mitigates Chronic Colitis in Rats: A Promising Multi-Pronged Approach Modulating Inflammasome Activity, Autophagy, and Pyroptosis.

Sameh Saber, Mohannad Mohammad S Alamri, Jaber Alfaifi, Lobna A Saleh, Sameh Abdel-Ghany, Adel Mohamed Aboregela, Alshaimaa A Farrag, Abdulrahman H Almaeen, Masoud I E Adam, AbdulElah Al Jarallah AlQahtani, Ali M S Eleragi, Mustafa Ahmed Abdel-Reheim, Heba A Ramadan, Osama A Mohammed.

  Ulcerative colitis is a chronic and incurable form of inflammatory bowel disease that can increase the risk of colitis-associated cancer and mortality. Limited treatment options are available for this condition, and the existing ones often come with non-tolerable adverse effects. This study is the first to examine the potential benefits of consuming (R,R)-BD-AcAc2, a type of ketone ester (KE), and intermittent fasting in treating chronic colitis induced by dextran sodium sulfate (DSS) in rats. We selected both protocols to enhance the levels of β-hydroxybutyrate, mimicking a state of nutritional ketosis and early ketosis, respectively. Our findings revealed that only the former protocol, consuming the KE, improved disease activity and the macroscopic and microscopic features of the colon while reducing inflammation scores. Additionally, the KE counteracted the DSS-induced decrease in the percentage of weight change, reduced the colonic weight-to-length ratio, and increased the survival rate of DSS-insulted rats. KE also showed potential antioxidant activities and improved the gut microbiome composition. Moreover, consuming KE increased the levels of tight junction proteins that protect against leaky gut and exhibited anti-inflammatory properties by reducing proinflammatory cytokine production. These effects were attributed to inhibiting NFκB and NLRP3 inflammasome activation and restraining pyroptosis and apoptosis while enhancing autophagy as revealed by reduced p62 and increased BECN1. Furthermore, the KE may have a positive impact on maintaining a healthy microbiome. To conclude, the potential clinical implications of our findings are promising, as (R,R)-BD-AcAc2 has a greater safety profile and can be easily translated to human subjects.

Keywords:  (R,R)-BD-AcAc2; NLRP3 inflammasome; autophagy; gut dysbiosis; ketone esters; pyroptosis; ulcerative colitis

DOI:  https://doi.org/10.3390/ph16070953
Biomed J. 2023 Jul 25. pii: S2319-4170(23)00073-2. [Epub ahead of print] 100636

Exercise, mitochondrial dysfunction and inflammasomes in skeletal muscle.

Mikhaela B Slavin, Priyanka Khemraj, David A Hood.

  In the broad field of inflammation, skeletal muscle is a tissue that is understudied. Yet it represents about 40% of body mass in non-obese individuals and is therefore of fundamental importance for whole body metabolism and health. This article provides an overview of the unique features of skeletal muscle tissue, as well as its adaptability to exercise. This ability to adapt, particularly with respect to mitochondrial content and function, confers a level of metabolic "protection" against energy consuming events, and adds a measure of quality control that determines the phenotypic response to stress. Thus, we describe the particular role of mitochondria in promoting inflammasome activation in skeletal muscle, contributing to muscle wasting and dysfunction in aging, disuse and metabolic disease. We will then discuss how exercise training can be anti-inflammatory, mitigating the chronic inflammation that is observed in these conditions, potentially through improvements in mitochondrial quality and function.

Keywords:  aging; exercise; inflammation; mitochondria; muscle disuse; skeletal muscle

DOI:  https://doi.org/10.1016/j.bj.2023.100636
Antioxidants (Basel). 2023 Jul 22. pii: 1471. [Epub ahead of print]12(7):

1,3-Butanediol Administration Increases β-Hydroxybutyrate Plasma Levels and Affects Redox Homeostasis, Endoplasmic Reticulum Stress, and Adipokine Production in Rat Gonadal Adipose Tissue.

Giuliana Panico, Gianluca Fasciolo, Vincenzo Migliaccio, Rita De Matteis, Lillà Lionetti, Gaetana Napolitano, Claudio Agnisola, Paola Venditti, Assunta Lombardi.

  Ketone bodies (KBs) are an alternative energy source under starvation and play multiple roles as signaling molecules regulating energy and metabolic homeostasis. The mechanism by which KBs influence visceral white adipose tissue physiology is only partially known, and our study aimed to shed light on the effects they exert on such tissue. To this aim, we administered 1,3-butanediol (BD) to rats since it rapidly enhances β-hydroxybutyrate serum levels, and we evaluated the effect it induces within 3 h or after 14 days of treatment. After 14 days of treatment, rats showed a decrease in body weight gain, energy intake, gonadal-WAT (gWAT) weight, and adipocyte size compared to the control. BD exerted a pronounced antioxidant effect and directed redox homeostasis toward reductive stress, already evident within 3 h after its administration. BD lowered tissue ROS levels and oxidative damage to lipids and proteins and enhanced tissue soluble and enzymatic antioxidant capacity as well as nuclear erythroid factor-2 protein levels. BD also reduced specific mitochondrial maximal oxidative capacity and induced endoplasmic reticulum stress as well as interrelated processes, leading to changes in the level of adipokines/cytokines involved in inflammation, macrophage infiltration into gWAT, adipocyte differentiation, and lipolysis.

Keywords:  Nrf2; ROS; adipokines; antioxidant enzymes; endoplasmic reticulum stress; ketone bodies; mitochondrial respiratory complexes

DOI:  https://doi.org/10.3390/antiox12071471
Res Sq. 2023 Jul 18. pii: rs.3.rs-3147009. [Epub ahead of print]

Hepatic ketogenesis regulates lipid homeostasis via ACSL1-mediated fatty acid partitioning.

Sadeesh Ramakrishnan, Raja Gopal Reddy Mooli, Yerin Han, Ericka Fiorenza, Suchita Kumar, Fiona Bello, Anoop Nallanagulagari, Shreya Karra, Lihong Teng, Michael Jurczak.

Liver-derived ketone bodies play a crucial role in fasting energy homeostasis by fueling the brain and peripheral tissues. Ketogenesis also acts as a conduit to remove excess acetyl-CoA generated from fatty acid oxidation and protects against diet-induced hepatic steatosis. Surprisingly, no study has examined the role of ketogenesis in fasting-associated hepatocellular lipid metabolism. Ketogenesis is driven by the rate-limiting mitochondrial enzyme 3-hydroxymethylglutaryl CoA synthase (HMGCS2) abundantly expressed in the liver. Here, we show that ketogenic insufficiency via disruption of hepatic HMGCS2 exacerbates liver steatosis in fasted chow and high-fat-fed mice. We found that the hepatic steatosis is driven by increased fatty acid partitioning to the endoplasmic reticulum (ER) for re-esterification via acyl-CoA synthetase long-chain family member 1 (ACSL1). Mechanistically, acetyl-CoA accumulation from impaired hepatic ketogenesis is responsible for the elevated translocation of ACSL1 to the ER. Moreover, we show increased ER-localized ACSL1 and re-esterification of lipids in human NASH displaying impaired hepatic ketogenesis. Finally, we show that L-carnitine, which buffers excess acetyl-CoA, decreases the ER-associated ACSL1 and alleviates hepatic steatosis. Thus, ketogenesis via controlling hepatocellular acetyl-CoA homeostasis regulates lipid partitioning and protects against hepatic steatosis.

DOI: https://doi.org/10.21203/rs.3.rs-3147009/v1
J Headache Pain. 2023 Jul 28. 24(1): 95

2:1 ketogenic diet and low-glycemic-index diet for the treatment of chronic and episodic migraine: a single-center real-life retrospective study.

Yan Tereshko, Simone Dal Bello, Cherubino Di Lorenzo, Sara Pez, Alice Pittino, Roberto Sartor, Francesca Filippi, Christian Lettieri, Enrico Belgrado, Riccardo Garbo, Giovanni Merlino, Gian Luigi Gigli, Mariarosaria Valente.

  AIMS: The evidence supporting the efficacy of dietary preventive therapy in migraine is rising, particularly regarding the ketogenic diet. However, less evidence exists for the Low-Glycemic Index Diet and the 2:1 KD. This retrospective single-center real-life study aims to evaluate the efficacy of a 2:1 ketogenic diet and a Low-Glycemic-index Diet in chronic and high-frequency episodic migraine.METHODS: Sixty patients with high-frequency episodic and chronic migraine were treated with either a Low-Glycemic-index diet (39 patients) or a 2:1 (21 patients) ketogenic diet for three months. We collected data on the migraine frequency and intensity and the MIDAS and HIT-6 scores through the headache diary. Anthropometric measurements (BMI, fat mass, free fat mass, and weight) were also collected and analyzed similarly. Data obtained at the baseline and after three months of each diet were compared.
RESULTS: Migraine intensity, frequency, MIDAS and HIT-6 scores, fat mass, weight, and BMI improved in both diet groups.
CONCLUSIONS: Both diets are effective in reducing migraine symptoms and migraine-related disability.

Keywords:  Headache; Ketogenic diet; Low-glycemic index diet; Migraine; Migraine prophylaxis

DOI:  https://doi.org/10.1186/s10194-023-01635-9
Eur J Pharmacol. 2023 Jul 24. pii: S0014-2999(23)00443-0. [Epub ahead of print] 175931

Research progress of NLRP3 inflammasome and its inhibitors with aging diseases.

Zhuo Yuan, Dongke Yu, Tingting Gou, Guoyuan Tang, Chun Guo, Jianyou Shi.

  In recent years, a new target closely linked to a variety of diseases has appeared in the researchers' vision, which is the NLRP3 inflammasome. With the deepening of the study of NLRP3 inflammasome, it was found that it plays an extremely important role in a variety of physiological pathological processes, and NLRP3 inflammasome was also found to be associated with some age-related diseases. It is associated with the development of insulin resistance, Alzheimer's disease, Parkinson's, cardiovascular aging, hearing and vision loss. At present, the only clinical approach to the treatment of NLRP3 inflammasome-related diseases is to use anti-IL-1β antibodies, but NLRP3-specific inhibitors may be better than the IL-1β antibodies. This article reviews the relationship between NLRP3 inflammasome and aging diseases: summarizes some of the relevant experimental results reported in recent years, and introduces the biological signals or pathways closely related to the NLRP3 inflammasome in a variety of aging diseases, and also introduces some promising small molecule inhibitors of NLRP3 inflammasome for clinical treatment, such as: ZYIL1, DFV890 and OLT1177, they have excellent pharmacological effects and good pharmacokinetics.

Keywords:  Aging damage to the reproductive system; Cardiovascular aging diseases; Diseases of aging; Inflammation; NLRP3 inflammasome; NLRP3 inhibitors; Neuronal atrophy

DOI:  https://doi.org/10.1016/j.ejphar.2023.175931
Antioxidants (Basel). 2023 Jul 07. pii: 1396. [Epub ahead of print]12(7):

Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects.

Pasquale Pagliaro, Claudia Penna.

  Myocardial ischemia-reperfusion injury (MIRI) is caused by several mechanisms, including the production of reactive oxygen species (ROS), altered cellular osmolarity, and inflammatory response. Calcium overload, altered oxygen levels, and mitochondrial ROS are also involved in these MIRI processes, resulting in the irreversible opening of the mitochondrial permeability transition pore (mPTP). These mechanisms and processes are associated with NLRP3 inflammasome priming and activation, which can also induce cell death by pyroptosis through the up-regulation of the caspase-1 pathway and IL-18 release. In addition, endothelial dysfunction, both in the presence and absence of MIRI, is also accompanied by altered oxygen levels, decreased nitric oxide production, and ROS overproduction, resulting in the expression of adhesion molecules and leukocyte infiltration in which the NLRP3 inflammasome plays a central role, thus contributing, through endothelial dysfunction, to the alteration of coronary flow, typical of ischemic heart disease. Given the intricate interrelationship between ROS and NLRP3, ROS inhibitors can reduce NLRP3 inflammasome activation, while NLRP3 inhibitors can reduce oxidative stress and inflammation. NLRP3 inhibitors have been intensively studied as anti-inflammatory agents in basic cardiovascular sciences. In this review, we analyze the interrelation between ROS and NLRP3 in ischemic heart disease and the effects of some NLRP3 inhibitors as possible therapeutic agents in this disease condition. All compounds considered in this review need larger studies to confirm their appropriate use in clinical scenarios as anti-ischemic drugs.

Keywords:  endothelial dysfunction; inflammation; ischemia/reperfusion injury; reactive oxygen species

DOI:  https://doi.org/10.3390/antiox12071396
Biomolecules. 2023 Jul 14. pii: 1133. [Epub ahead of print]13(7):

The Potential of Fasting-Mimicking Diet as a Preventive and Curative Strategy for Alzheimer's Disease.

Virginia Boccardi, Martina Pigliautile, Anna Giulia Guazzarini, Patrizia Mecocci.

  This review examines the potential of fasting-mimicking diets (FMDs) in preventing and treating Alzheimer's disease (AD). FMDs are low-calorie diets that mimic the physiological and metabolic effects of fasting, including the activation of cellular stress response pathways and autophagy. Recent studies have shown that FMDs can reduce amyloid-beta accumulation, tau phosphorylation, and inflammation, as well as improve cognitive function in animal models of AD. Human studies have also reported improvements in AD biomarkers, cognitive functions, and subjective well-being measures following FMDs. However, the optimal duration and frequency of FMDs and their long-term safety and efficacy remain to be determined. Despite these uncertainties, FMDs hold promise as a non-pharmacological approach to AD prevention and treatment, and further research in this area is warranted.

Keywords:  Alzheimer; diet; health span; nutrition; prevention

DOI:  https://doi.org/10.3390/biom13071133