bims-kimdis 2023-10-29 papers

bims-kimdis

Biomed News

on Ketones, inflammation and mitochondria in disease

Issue of 2023‒10‒29
sixteen papers selected by
Matías Javier Monsalves Álvarez

The ketone body β-hydroxybutyrate shifts microglial metabolism and suppresses amyloid-β oligomer-induced inflammation in human microglia.
Ketone Bodies in Diabetes Mellitus: Friend or Foe?
Ketogenic diet reduces a neurobiological craving signature in alcohol use disorder.
Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate.
Acute effects of β-hydroxybutyrate on left ventricular function in young, healthy adults.
Dose-Dependent Beneficial Effect of Ketone Supplement-Evoked Ketosis on Anxiety Level in Female WAG/Rij Rats: Sometimes Less Is More.
The Effect of Three Different Ketogenic Diet Protocols on Migraine and Fatigue in Chronic and High-Frequency Episodic Migraine: A Pilot Study.
Butyrate ameliorated the intestinal barrier dysfunction and attenuated acute pancreatitis in mice fed with ketogenic diet.
Cardiorenal ketone metabolism: a positron emission tomography study in healthy humans.
Study: Carbohydrate Quality Matters for Body Weight.
Muscle Mass and Strength Gains Following Resistance Exercise Training in Older Adults 65-75 Years and Older Adults Above 85 Years.
Glucose tolerance status associates with improvements in cognitive function following high-intensity exercise in adults with obesity.
Oral ketamine may offer a solution to the ketamine conundrum.
Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome.
Mitochondria as a target for exercise-mitigated type 2 diabetes.
Carbohydrates: friend or foe to post-exercise hunger?

FASEB J. 2023 11;37(11): e23261

The ketone body β-hydroxybutyrate shifts microglial metabolism and suppresses amyloid-β oligomer-induced inflammation in human microglia.

Lee-Way Jin, Jacopo Di Lucente, Ulises Ruiz Mendiola, Nopparat Suthprasertporn, Alexey Tomilov, Gino Cortopassi, Kyoungmi Kim, Jon J Ramsey, Izumi Maezawa.

  Fatty acids are metabolized by β-oxidation within the "mitochondrial ketogenic pathway" (MKP) to generate β-hydroxybutyrate (BHB), a ketone body. BHB can be generated by most cells but largely by hepatocytes following exercise, fasting, or ketogenic diet consumption. BHB has been shown to modulate systemic and brain inflammation; however, its direct effects on microglia have been little studied. We investigated the impact of BHB on Aβ oligomer (AβO)-stimulated human iPS-derived microglia (hiMG), a model relevant to the pathogenesis of Alzheimer's disease (AD). HiMG responded to AβO with proinflammatory activation, which was mitigated by BHB at physiological concentrations of 0.1-2 mM. AβO stimulated glycolytic transcripts, suppressed genes in the β-oxidation pathway, and induced over-expression of AD-relevant p46Shc, an endogenous inhibitor of thiolase, actions that are expected to suppress MKP. AβO also triggered mitochondrial Ca2+ increase, mitochondrial reactive oxygen species production, and activation of the mitochondrial permeability transition pore. BHB potently ameliorated all the above mitochondrial changes and rectified the MKP, resulting in reduced inflammasome activation and recovery of the phagocytotic function impaired by AβO. These results indicate that microglia MKP can be induced to modulate microglia immunometabolism, and that BHB can remedy "keto-deficiency" resulting from MKP suppression and shift microglia away from proinflammatory mitochondrial metabolism. These effects of BHB may contribute to the beneficial effects of ketogenic diet intervention in aged mice and in human subjects with mild AD.

Keywords:  Alzheimer's; amyloid; inflammation; ketone; microglia; mitochondria; phagocytosis

DOI:  https://doi.org/10.1096/fj.202301254R
Nutrients. 2023 Oct 16. pii: 4383. [Epub ahead of print]15(20):

Ketone Bodies in Diabetes Mellitus: Friend or Foe?

Stavroula Veneti, Maria G Grammatikopoulou, Evangelia Kintiraki, Gesthimani Mintziori, Dimitrios G Goulis.

  In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner.

Keywords:  acetoacetate; carbohydrate restriction; low glycemic index; low-carbohydrate diet; middle-chain triglycerides; obesity; prediabetes; weight loss; β-hydroxybutyrate

DOI:  https://doi.org/10.3390/nu15204383
medRxiv. 2023 Sep 26. pii: 2023.09.25.23296094. [Epub ahead of print]

Ketogenic diet reduces a neurobiological craving signature in alcohol use disorder.

Corinde E Wiers, Peter Manza, Gene-Jack Wang, Nora D Volkow.

Background and Aims: Increasing evidence suggests that a ketogenic (high-fat, low-carbohydrate) diet intervention reduces alcohol withdrawal severity and alcohol craving in individuals with alcohol use disorder (AUD) by shifting brain energetics from glucose to ketones. We hypothesized that the ketogenic diet would reduce a brain craving signature when individuals undergoing alcohol detoxification treatment were exposed to alcohol cues.Methods: We performed a secondary analysis of functional magnetic resonance data of n=33 adults with an AUD were randomized to a ketogenic diet (n=19) or a standard American diet (n=14) and underwent three weeks of inpatient alcohol detoxification treatment. Once per week, participants performed an alcohol cue-reactivity paradigm with functional magnetic resonance imaging. We extracted brain responses to food and alcohol cues and quantified the degree to which each set of brain images shared a pattern of activation with a recently validated 'Neurobiological Craving Signature' (NCS). We then performed a group-by-time repeated measures ANOVA to test for differences in craving signature expression between the dietary groups over the three-week treatment period. We also correlated these expression patterns with self-reported wanting ratings for alcohol cues.
Results: For alcohol relative to food cues, there was a main effect of group, such that the ketogenic diet group showed lower NCS expression across all three weeks of treatment. The main effect of time and the group-by-time interaction were not significant. Self-reported wanting for alcohol cues reduced with KD compared to SA but did not correlate with the NCS score.
Conclusions: A ketogenic diet reduces self-reported alcohol wanting, and induced lower brain craving signatures to alcohol cues during inpatient treatment for AUD.

DOI: https://doi.org/10.1101/2023.09.25.23296094
Nutrients. 2023 Oct 18. pii: 4427. [Epub ahead of print]15(20):

Ketogenic Diet Exacerbates L-Arginine-Induced Acute Pancreatitis and Reveals the Therapeutic Potential of Butyrate.

He Xia, Jing Guo, Jian Shen, Shiman Jiang, Shengyi Han, Lanjuan Li.

  The ketogenic diet (KD) has emerged as a popular weight-loss regimen in recent years. However, it has been confirmed to elicit a mild inflammatory response in the intestinal epithelium and exacerbate various digestive disorders. The severity of acute pancreatitis (AP) is closely associated with the permeability of the intestinal epithelium and gut microbiota, yet the impact of KD on acute pancreatitis remains unclear. In this study, we induced acute pancreatitis using L-arginine in mice fed with KD. The consumption of KD resulted in an elevation of lipopolysaccharide-binding protein (LBP), accompanied by upregulated cytokines (IL-1a, IL-5, IL-12, MIP-1a, and Rantes) and dysfunction of the intestinal barrier both in control and AP groups. The bloom of Lachnospirales and Erysipelotrichales was observed as a specific profile of gut microbiota in KD-fed mice with AP, along with downregulation of carbohydrate metabolism and depletion of short-chain fatty acids (SCFAs). Antibiotic decontamination reduced the cytokine storm and tissue necrosis but did not significantly improve the integrity of the intestinal barrier in KD-fed mice with AP. The overgrowth of Mycoplasmatales in feces and Enterobacterales in colonic tissue appears to explain the limitation of antibiotic treatment to aggravate acute pancreatitis. Butyrate supplementation attenuated the depletion of SCFAs, promoted the intestinal barrier, and reduced the necrotic area in AP mice. The bloom of Bacteroidales and the correlated increase in tryptophan metabolism explain the therapeutic potential of butyrate supplements for acute pancreatitis. In conclusion, our findings suggest that the ketogenic diet exacerbates acute pancreatitis through its impact on the gut microbiota and subsequent disruption of the intestinal barrier, while butyrate supplementation reverses this effect.

Keywords:  L-arginine; acute pancreatitis; butyrate; ketogenic diet

DOI:  https://doi.org/10.3390/nu15204427
J Appl Physiol (1985). 2023 Oct 26.

Acute effects of β-hydroxybutyrate on left ventricular function in young, healthy adults.

Andrew P Oneglia, Benjamin Young, Daisha J Cipher, Vlad Zaha, Michael D Nelson.

  Interest in ketones as a cardiac 'super fuel' has grown significantly following reports of a marked increase in cardiac output following exogenous ketone administration in heart failure. However, the extent to which this increase in cardiac output is related to changes in cardiac contractility, and dependent on the presence of heart failure, remains incompletely understood. Therefore, we performed a randomized, double-blind, placebo-controlled study of oral ketone ester in young healthy volunteers. Baseline cardiac magnetic resonance imaging was performed and repeated every 15 minutes for 60 minutes after ketone and placebo ingestion to assess changes in left ventricular function. As expected, circulating β-hydroxybutyrate increased rapidly after ketone ingestion, but did not change with placebo (interaction: p<0.001). Consistent with prior investigations, ketone ingestion resulted in an average 1 L/min increase in cardiac output after 60 minutes that did not occur with placebo (interaction: p=0.026). This increase in cardiac output was primarily driven by an increase in heart rate after ketone ingestion (interaction: p=0.018), with only a modest increase in stroke volume (interaction: p=0.037). Changes in left ventricular strain and twist mechanics were limited. Taken together, the increase in cardiac output following an acute elevation in circulating β-hydroxybutyrate is primarily driven by changes in cardiac chronotropy, with minimal inotropic contribution.

Keywords:  heart function; ketones; magnetic resonance imaging

DOI:  https://doi.org/10.1152/japplphysiol.00630.2023
Nutrients. 2023 Oct 18. pii: 4412. [Epub ahead of print]15(20):

Dose-Dependent Beneficial Effect of Ketone Supplement-Evoked Ketosis on Anxiety Level in Female WAG/Rij Rats: Sometimes Less Is More.

Enikő Rauch, Csilla Ari, Zsolt Kovács.

  While one-third of the population can be affected by anxiety disorders during their lifetime, our knowledge of the pathophysiology of these disorders is far from complete. Previously, it has been demonstrated in male animals that exogenous ketone supplement-evoked ketosis can decrease anxiety levels in preclinical rodent models, such as Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Thus, in this study, we investigated whether intragastric gavage of the exogenous ketone supplement KEMCT (mix of 1,3-butanediol-acetoacetate diester/ketone ester/KE and medium-chain triglyceride/MCT oil in 1:1 ratio) for 7 days can alter the anxiety levels of female WAG/Rij rats using the light-dark box (LDB) test. We demonstrated that a lower dose of KEMCT (3 g/kg/day) increased blood R-βHB (R-β-hydroxybutyrate) levels and significantly decreased anxiety levels (e.g., increased the time spent in the light compartment) in female WAG/Rij rats on the seventh day of administration. Although the higher KEMCT dose (5 g/kg/day) increased blood R-βHB levels more effectively, compared with the lower KEMCT dose, anxiety levels did not improve significantly. We conclude that ketone supplementation might be an effective strategy to induce anxiolytic effects not only in male but also in female WAG/Rij rats. However, these results suggest that the optimal level may be moderately, not highly, elevated blood R-βHB levels when the goal is to alleviate symptoms of anxiety. More studies are needed to understand the exact mechanism of action of ketone supplementation on anxiety levels and to investigate their use in other animal models and humans for the treatment of anxiety disorders and other mental health conditions.

Keywords:  LDB test; anxiety; exogenous ketone supplement; female WAG/Rij rat; mental health

DOI:  https://doi.org/10.3390/nu15204412
Nutrients. 2023 Oct 11. pii: 4334. [Epub ahead of print]15(20):

The Effect of Three Different Ketogenic Diet Protocols on Migraine and Fatigue in Chronic and High-Frequency Episodic Migraine: A Pilot Study.

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

  AIMS: We aimed to evaluate the efficacy of three different ketogenic diets on migraine and fatigue in chronic and high-frequency episodic migraineurs.METHODS: 76 patients with migraine were treated with the KD for at least three months. Three different KD protocols were used (2:1 KD, LGID, and VLCKD). We evaluated the fatigue severity scale (FSS), migraine frequency, migraine intensity, MIDAS, and HIT-6 at the baseline and 3-month follow-up, and we compared the results. We also correlated the mean FSS reduction with the mean migraine frequency, migraine intensity, BMI, fat mass, free-fat mass, MIDAS, and HIT-6 reduction.
RESULTS: FSS improved from 4.977 ± 1.779 to 3.911 ± 1.779 at the 3-month follow-up (p < 0.001). This improvement was significant in both high-frequency and chronic migraineurs. Moreover, the three KD protocols effectively improved migraine intensity, frequency, MIDAS, and HIT-6. There was a mild correlation between mean FSS reduction (p < 0.001), mean MIDAS (p = 0.001), and HIT-6 (p = 0.002) reduction.
CONCLUSIONS: The VLCKD, LGID, and 2:1 KD may improve migraine intensity, frequency, and fatigue in chronic and high-frequency episodic migraineurs.

Keywords:  KD; LGID; VLCKD; fatigue; headache; ketogenic diet; migraine

DOI:  https://doi.org/10.3390/nu15204334
Life Sci. 2023 Oct 20. pii: S0024-3205(23)00823-8. [Epub ahead of print] 122188

Butyrate ameliorated the intestinal barrier dysfunction and attenuated acute pancreatitis in mice fed with ketogenic diet.

He Xia, Jing Guo, Jian Shen, Shiman Jiang, Shengyi Han, Lanjuan Li.

  Butyrate, a short-chain fatty acid (SCFA), has demonstrated significant efficacy in preventing colitis-associated inflammation. Acute pancreatitis is an acute gastrointestinal disorder characterized by increased systemic inflammation, bacterial translocation, and disrupted intestinal barrier. However, the effects and mechanisms of butyrate in attenuating acute pancreatitis remain unclear. In this study, we established two mouse models of acute pancreatitis induced by cerulein (Cer) and taurocholate (TA), which were further exacerbated by a ketogenic diet (KD). The results suggested that butyrate supplementation effectively reduced mortality rates, systemic inflammation, and intestinal barrier disruption caused by Cer- and TA-induced acute pancreatitis in mice fed a KD. Furthermore, we observed a significant reduction in gut microbiota diversity as well as overgrowth of Lachnospirales and Erysipelotrichales along with depletion of SCFAs in mice fed a KD, and these alterations were reversed by butyrate supplement. To evaluate the role of microbiota and butyrate supplement, we conducted germ-depletion trials by antibiotics. The results showed that while systemic inflammation was attenuated in mice with TA-induced pancreatitis following antibiotic treatment, the reduction in mortality remained inconclusive (p = 0.055). Importantly, the key differential change between antibiotic treatment and butyrate supplementation was found to be related to intestinal barrier dysfunction and repairment. These results suggest that butyrate plays a central role in mitigating acute pancreatitis through amelioration of intestinal barrier dysfunction.

Keywords:  Acute pancreatitis; Butyrate; Gut microbiota; Intestinal barrier; Ketogenic diet

DOI:  https://doi.org/10.1016/j.lfs.2023.122188
Front Physiol. 2023 ;14 1280191

Cardiorenal ketone metabolism: a positron emission tomography study in healthy humans.

Bernard Cuenoud, Etienne Croteau, Valérie St-Pierre, Gabriel Richard, Mélanie Fortier, Camille Vandenberghe, André C Carpentier, Stephen C Cunnane.

  Ketones are alternative energy substrates for the heart and kidney but no studies have investigated their metabolism simultaneously in both organs in humans. The present double tracer positron emission tomography (PET) study evaluated the organ distribution and basal kinetic rates of the radiolabeled ketone, 11C-acetoacetate (11C-AcAc), in the heart and kidney compared to 11C-acetate (11C-Ac), which is a well-validated metabolic radiotracer. Both tracers were highly metabolized by the left ventricle and the renal cortex. In the heart, kinetic rates were similar for both tracers. But in the renal cortex, uptake of 11C-Ac was higher compared to 11C-AcAc, while the reverse was observed for the clearance. Interestingly, infusion of 11C-AcAc led to a significantly delayed release of radioactivity in the renal medulla and pelvis, a phenomenon not observed with 11C-Ac. This suggests an equilibrium of 11C-AcAc with the other ketone, 11C-D-beta-hydroxybutyrate, and a different clearance profile. Overall, this suggests that in the kidney, the absorption and metabolism of 11C-AcAc is different compared to 11C-Ac. This dual tracer PET protocol provides the opportunity to explore the relative importance of ketone metabolism in cardiac and renal diseases, and to improve our mechanistic understanding of new metabolic interventions targeting these two organs.

Keywords:  11C-acetate; 11C-acetoacetate; beta-hydroxybutyrate; cardiorenal; heart; ketone; kidney; metabolism

DOI:  https://doi.org/10.3389/fphys.2023.1280191
JAMA. 2023 Oct 25.

Study: Carbohydrate Quality Matters for Body Weight.

Emily Harris.

DOI: https://doi.org/10.1001/jama.2023.20629
Int J Sport Nutr Exerc Metab. 2023 Oct 24. 1-9

Muscle Mass and Strength Gains Following Resistance Exercise Training in Older Adults 65-75 Years and Older Adults Above 85 Years.

Gabriel Nasri Marzuca-Nassr, Andrea Alegría-Molina, Yuri SanMartín-Calísto, Macarena Artigas-Arias, Nolberto Huard, Jorge Sapunar, Luis A Salazar, Lex B Verdijk, Luc J C van Loon.

  Resistance exercise training (RET) can be applied effectively to increase muscle mass and function in older adults (65-75 years). However, it has been speculated that older adults above 85 years are less responsive to the benefits of RET. This study compares the impact of RET on muscle mass and function in healthy older adults 65-75 years versus older adults above 85 years. We subjected 17 healthy older adults 65-75 years (OLDER 65-75, n = 13/4 [female/male]; 68 ± 2 years; 26.9 ± 2.3 kg/m2) and 12 healthy older adults above 85 years (OLDER 85+, n = 7/5 [female/male]; 87 ± 3 years; 26.0 ± 3.6 kg/m2) to 12 weeks of whole-body RET (three times per week). Prior to, and after 6 and 12 weeks of training, quadriceps and lumbar spine vertebra 3 muscle cross-sectional area (computed tomography scan), whole-body lean mass (dual-energy X-ray absorptiometry scan), strength (one-repetition maximum test), and physical performance (timed up and go and short physical performance battery) were assessed. Twelve weeks of RET resulted in a 10% ± 4% and 11% ± 5% increase in quadriceps cross-sectional area (from 46.5 ± 10.7 to 51.1 ± 12.1 cm2, and from 38.9 ± 6.1 to 43.1 ± 8.0 cm2, respectively; p < .001; η2 = .67); a 2% ± 3% and 2% ± 3% increase in whole-body lean mass (p = .001; η2 = .22); and a 38% ± 20% and 46% ± 14% increase in one-repetition maximum leg extension strength (p < .001; η2 = .77) in the OLDER 65-75 and OLDER 85+ groups, respectively. No differences in the responses to RET were observed between groups (Time × Group, all p > .60; all η2 ≤ .012). Physical performance on the short physical performance battery and timed up and go improved (both p < .01; η2 ≥ .22), with no differences between groups (Time × Group, p > .015; η2 ≤ .07). Prolonged RET increases muscle mass, strength, and physical performance in the aging population, with no differences between 65-75 years and 85+ years older adults.

Keywords:  aging; elderly; resistance training; sarcopenia; skeletal muscle

DOI:  https://doi.org/10.1123/ijsnem.2023-0087
Physiol Behav. 2023 Oct 25. pii: S0031-9384(23)00314-1. [Epub ahead of print] 114389

Glucose tolerance status associates with improvements in cognitive function following high-intensity exercise in adults with obesity.

Gregory N Ruegsegger, Emily R Ekholm, Chandler E Monroe, Chapin I Rappaport, Rocco D Huppert, Caleb R Anton, Mia J Ferguson.

  PURPOSE: Obesity, insulin resistance (IR), and proinflammatory cytokines associate with cognitive decline. Numerous studies document cognitive benefits of acute exercise bouts in lean individuals. However, how co-morbidities such as obesity and IR influence cognitive changes induced by acute exercise is unclear. We examined the effects of acute high-intensity aerobic exercise on cognitive function in age-matched and BMI-matched obese adults with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) and in lean, NGT adults.METHODS: 49 adults (15 Lean, 18 Obese-NGT, 16 Obese-IGT) performed one session of high-intensity interval exercise (four cycles of 4-min at 75% Wmax with 3-min rest). Cognitive function testing and blood sampling were performed pre- and post-exercise.
RESULTS: Following exercise, measurements of executive function and working memory were improved in Lean and Obese-NGT (p < 0.05), but not Obese-IGT. Changes in cognitive function following exercise negatively correlated with 2-hr glucose during an OGTT after controlling for body weight and body composition (rp = -0.40, p = 0.007). Serum levels of inflammatory cytokines IL-6 and CRP remained increased 60-minutes post-exercise in Obese-IGT, but not in Lean or Obese-NGT, which positively associated with 2-hr glucose during an OGTT (p < 0.01) and negatively with changes in cognitive function following exercise (p < 0.01). Greater insulin levels in Obese-IGT post-exercise also negatively correlated with changes in cognitive function following exercise (p < 0.01).
CONCLUSION: Improvements in cognition following acute high-intensity exercise positively associate with glucose tolerance, independent of body weight and body composition. Further, poorer changes in cognitive performance following exercise associate with persistent peripheral inflammation.

Keywords:  Insulin resistance; cognition; exercise; inflammation; prediabetes

DOI:  https://doi.org/10.1016/j.physbeh.2023.114389
Psychopharmacology (Berl). 2023 Oct 26.

Oral ketamine may offer a solution to the ketamine conundrum.

Megan Dutton, Adem T Can, Jim Lagopoulos, Daniel F Hermens.

  Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative. Emerging evidence regarding the efficacy and tolerability of oral ketamine suggests that it may be a favourable route of administration, as it appears to obtain similarly beneficial treatment effects, but without the cost and medical resources required in parenteral dosing. The pharmacological effects may be due to the active metabolite norketamine, which has been found to be at substantially higher levels via oral dosing, most likely due to first-pass clearance. Despite bioavailability and peak plasma concentrations both being lower than when administered parenterally, evidence suggests that low-dose oral ketamine is clinically effective in treating pain. This may also be due to the actions of norketamine and therefore, its relevance to the mental health context is explored in this narrative review.

Keywords:  Bioavailability; Clinical use; Efficacy; Norketamine; Oral ketamine; Pharmacokinetics

DOI:  https://doi.org/10.1007/s00213-023-06480-x
Brain Sci. 2023 Sep 28. pii: 1383. [Epub ahead of print]13(10):

Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome.

Abdulhadi Bima, Basmah Eldakhakhny, Aliaa A Alamoudi, Zuhier Awan, Abrar Alnami, Salwa Mohamed Abo-Elkhair, Hussein Sakr, Fatma Mohamed Ghoneim, Ayman Elsamanoudy.

  Brain insulin resistance is linked to metabolic syndrome (MetS). A low-carbohydrate, high-fat (LCHF) diet has been proposed to have a protective effect. Therefore, this study aimed to investigate the brain insulin resistance markers in a rat animal model of MetS and the protective effects of the LCHF diet. Four groups of male rats (10/group) were created. Group I (Control) was fed a regular diet. Groups II-IV were injected with dexamethasone (DEX) to induce MetS. Group II received DEX with a regular diet. Group III (DEX + LCHF) rates were fed a low-carbohydrate, high-fat diet, while Group IV (DEX + HCLF) rats were fed a high-carbohydrate, low-fat (HCLF) diet. At the end of the four-week experiment, HOMA-IR was calculated. Moreover, cerebral gene expression analysis of S-100B, BDNF, TNF-α, IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, Bax, Bcl-2, and caspase-3 was carried out. In the DEX group, rats showed a significant increase in the HOMA-IR and a decrease in the gene expression of IGF-1, IGF-1 R, IGFBP-2, IGFBP-5, BDNF, and Bcl2, with a concomitant rise in S100B, TNF-α, Bax, and caspase-3. The LCHF diet group showed a significantly opposite effect on all parameters. In conclusion, MetS is associated with dysregulated cerebral gene expression of BDNF, S100B, and TNF-α and disturbed IGF-1 signaling, with increased apoptosis and neuroinflammation. Moreover, the LCHF diet showed a protective effect, as evidenced by preservation of the investigated biochemical and molecular parameters.

Keywords:  BDNF; Bax; Bcl-2; IGF-1; IGF-1R; IGFBP-2; IGFBP-5; S100B; TNF-α; brain insulin resistance; caspase-3; low carbohydrate-high fat diet; metabolic syndrome

DOI:  https://doi.org/10.3390/brainsci13101383
J Mol Histol. 2023 Oct 24.

Mitochondria as a target for exercise-mitigated type 2 diabetes.

Jingjing Tian, Jingcheng Fan, Tan Zhang.

  Type 2 diabetes mellitus (T2DM) is one of most common metabolic diseases and continues to be a leading cause of death worldwide. Although great efforts have been made to elucidate the pathogenesis of diabetes, the underlying mechanism still remains unclear. Notably, overwhelming evidence has demonstrated that mitochondria are tightly correlated with the development of T2DM, and the defects of mitochondrial function in peripheral insulin-responsive tissues, such as skeletal muscle, liver and adipose tissue, are crucial drivers of T2DM. Furthermore, exercise training is considered as an effective stimulus for improving insulin sensitivity and hence is regarded as the best strategy to prevent and treat T2DM. Although the precise mechanisms by which exercise alleviates T2DM are not fully understood, mitochondria may be critical for the beneficial effects of exercise.

Keywords:  Adipose tissue; Exercise; Insulin resistance; Liver; Mitochondria; Skeletal muscle; T2DM

DOI:  https://doi.org/10.1007/s10735-023-10158-1
J Physiol. 2023 Oct 27.

Carbohydrates: friend or foe to post-exercise hunger?

Alice Irving, Phoebe Thomas, Christina Young, Sally Handford.



Keywords:  ad libitum; appetite suppression; carbohydrate; exercise; hormones; metabolism

DOI:  https://doi.org/10.1113/JP285386