bims-kimdis 2023-03-05 papers

Open Life Sci. 2023 ;18(1): 20220570

Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice.

Ketogenic diet (KD) has been proven to be an optional avenue in weight control. However, the impacts of KD on muscle strength and exercise endurance remain unclear. In this study, mice were randomly allocated to normal diet and KD groups to assess their exercise tolerance and transcriptomic changes of the gastrocnemius. KD suppressed body-weight and glucose levels and augmented blood ketone levels of mice. The total cholesterol, free fatty acids, and β-hydroxybutyric acid levels were higher and triglycerides and aspartate aminotransferase levels were lower in KD group. There was no notable difference in running distance/time and weight-bearing swimming time between the two groups. Furthermore, KD alleviated the protein levels of PGC-1α, p62, TnI FS, p-AMPKα, and p-Smad3, while advancing the LC3 II and TnI SS protein levels in the gastrocnemius tissues. RNA-sequencing found that 387 differentially expressed genes were filtered, and Cpt1b, Acadl, Eci2, Mlycd, Pdk4, Ptprc, C1qa, Emr1, Fcgr3, and Ctss were considered to be the hub genes. Our findings suggest that KD effectively reduced body weight but did not affect skeletal muscle strength and exercise endurance via AMPK/PGC-1α, Smad3, and p62/LC3 signaling pathways and these hub genes could be potential targets for muscle function in KD-treated mice.

Keywords: exercise tolerance; high-throughput sequencing; ketogenic diet; lipid metabolism

DOI: https://doi.org/10.1515/biol-2022-0570

J Diet Suppl. 2023 Feb 27. 1-15

The Effect of Novel Exogenous Ketone Supplements on Blood Beta-Hydroxybutyrate and Glucose.

Kaja Falkenhain, Ali Daraei, Jonathan P Little.

Exogenous ketone monoesters can raise blood β-OHB and lower glucose without other nutritional modifications or invasive procedures. However, unpleasant taste and potential gastrointestinal discomfort may make adherence to supplementation challenging. Two novel ketone supplements promise an improved consumer experience but differ in their chemical properties; it is currently unknown how these affect blood β-OHB and blood glucose compared to the ketone monoester. In a double-blind randomized cross-over pilot study, N=12 healthy individuals (29 ± 5 years, BMI = 25 ± 4 kg/m2, 42% female) participated in three experimental trials with a different ketone supplement providing 10 grams of active ingredient in each; (i) the monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, (ii) D-β-hydroxybutyric acid with R-1,3-butanediol, and (iii) R-1,3-butanediol. Blood β-OHB and glucose were measured via finger prick capillary blood samples at baseline and across 240 minutes post-supplementation. Supplement acceptability, hunger, and gastrointestinal distress were assessed via questionnaires. β-OHB was elevated compared to baseline in all conditions. Total and incremental area under the curve (p < 0.05) and peak β-OHB (p < 0.001) differed between conditions with highest values seen in the ketone monoester condition. Blood glucose was reduced after consumption of each supplement, with no differences in total and incremental area under the curve across supplements. Supplement acceptability was greatest for D-β-hydroxybutyric acid with R-1,3-butanediol, with no effect on hunger or evidence of gastrointestinal distress across all supplements. All ketone supplements tested raised β-OHB with highest values seen after ketone monoester ingestion. Blood glucose was lowered similarly across the assessed time frame with all three supplements.

Keywords: Beta-hydroxybutyrate; blood glucose; ketone ester; ketones; ketosis

DOI: https://doi.org/10.1080/19390211.2023.2179152

Exp Physiol. 2023 Feb 26.

Natural killer cell subset count and antigen-stimulated activation in response to exhaustive running following adaptation to a ketogenic diet.

David M Shaw, Lauren Keaney, Ed Maunder, Deborah K Dulson.

NEW FINDINGS: What is the central question of this study? Does a ketogenic diet (KD) modulate circulating counts of natural killer (NK) cells, including CD56bright and CD56dim subsets, and their ability to activate (CD69 expression) following in vitro antigen stimulation in response to exhaustive moderate-intensity exercise? What is the main finding and its importance? The KD amplified the biphasic exercise-induced NK cell response due to a greater mobilisation of the cytotoxic CD56dim subset but did not alter NK cell CD69 expression. The KD appears to modulate exercise-induced circulating NK cell mobilisation and egress, but not antigen-stimulated circulating NK cell activation.
ABSTRACT: We investigated the effect of a 31-day ketogenic diet (KD) compared with a habitual, carbohydrate (CHO)-based diet on total circulating natural killer (NK) CD3- CD56+ , dim and bright subset count, and antigen-stimulated CD3- CD56+ cell activation (CD69+ ) in response to exhaustive running. In a randomised, repeated-measures, cross-over study, eight trained, male endurance athletes ingested a 31-day low-CHO KD or their habitual diet (HD). On day 31, participants ran to exhaustion at 70% V̇O2max$\dot{V}_{{\rm{O}}_{2}{\rm{max}}}$ (∼3.5-4 h, ∼45-50 km). A low-CHO (<10 g) meal was ingested prior to the KD trial, with fat ingested during exercise. A high-CHO (2 g kg-1 ) meal was ingested prior to the HD trial, with CHO (∼55 g h-1 ) ingested during exercise. Venous blood samples were collected at pre-exercise, post-exercise and 1 h post-exercise. The KD amplified the classical exercise-induced biphasic CD3- CD56+ cell response by increasing the post-exercise counts (P = 0.0004), which appeared to be underpinned by the cytotoxic CD3- CD56dim subset (main effect of time point, P < 0.0001). The KD had no effect on NK cells' expression of CD69 or their geometric mean fluorescence intensity of CD69 expression, either for unstimulated or for antigen-stimulated NK cells (all P > 0.05). In conclusion, adaptation to a KD may alter the number of circulating NK cells but not their ability to activate to an antigenic challenge.

Keywords: CD56; CD69; endurance; exercise; flow cytometry; ketosis; lymphocytes

DOI: https://doi.org/10.1113/EP090729

Eur J Nucl Med Mol Imaging. 2023 Mar 03.

Regional brain glucose metabolism is differentially affected by ketogenic diet: a human semiquantitative positron emission tomography.

Tatiana Horowitz, Emilie Doche, Mary Philip, Serge Cammilleri, Laurent Suissa, Eric Guedj.

PURPOSE: Ketogenic diet (KD) is recommended to avoid intense [18F]FDG myocardial physiologic uptake in PET imaging. Neuroprotective and anti-seizure effects of KD have been suggested, but their mechanisms remain to be elucidated. This [18F]FDG PET study aims to evaluate the effect of KD on glucose brain metabolism.
METHOD: Subjects who underwent KD prior to whole-body and brain [18F]FDG PET between January 2019 and December 2020 in our department for suspected endocarditis were retrospectively included. Myocardial glucose suppression (MGS) on whole-body PET was analyzed. Patients with brain abnormalities were excluded. Thirty-four subjects with MGS (mean age: 61.8 ± 17.2 years) were included in the KD population, and 14 subjects without MGS were considered for a partial KD group (mean age: 62.3 ± 15.1 years). Brain SUVmax was first compared between these two KD groups to determine possible global uptake difference. Semiquantitative voxel-based intergroup analyses were secondarily performed to determine possible inter-regional differences by comparing KD groups with and without MGS, separately, to 27 healthy subjects fasting for at least 6 h (mean age of 62.4 ± 10.9 years), and KD groups between them (p-voxel < 0.001, and p-cluster < 0.05, FWE-corrected).
RESULTS: A 20% lower brain SUVmax was found in subjects under KD with MGS in comparison to those without MGS (Student's t-test, p = 0.02). Whole-brain voxel-based intergroup analysis revealed that patients under KD with and without MGS had relative hypermetabolism of limbic regions including medial temporal cortices and cerebellum lobes and relative hypometabolism of bilateral posterior regions (occipital), without significant difference between them.
CONCLUSION: KD globally reduces brain glucose metabolism but with regional differences, requiring special attention to clinical interpretation. On a pathophysiological perspective, these findings could help understand underlying neurological effects of KD through possible decrease of oxidative stress in posterior regions and functional compensation in the limbic regions.

Keywords: Brain PET; Ketogenic diet; Ketone; Metabolism; PET

DOI: https://doi.org/10.1007/s00259-023-06156-w