Background and objective:Metabolic associated fatty liver disease(MAFLD)is associated with abnormal lipid metabolism.Mitochondrial dysfunction is considered an important factor in the onset of MAFLD,whereas altered fatty acid composition has been linked to the severity of the disease.Tetradecylthio-acetic acid(TTA),shown to induce mitochondrial proliferation and alter the fatty acid composition,was used to delay the accumulation of hepatic triacylglycerol.This study aimed to evaluate how impaired mitochondrial fatty acid beta-oxidation affects fatty acid composition by incorporating meldonium into a high-carbohydrate diet. Methods:C57BL/6 mice(n=40)were fed high-carbohydrate diets supplemented with meldonium,TTA,or a combination of meldonium and TTA for 21 days.Lipid levels were determined in liver samples,and fatty acid composition was measured in both liver and plasma samples.Additionally,desaturase and elongase activities were estimated.The hepatic activities and gene expression levels of enzymes involved in fatty acid metabolism were measured in liver samples,whereas carnitines,their precursors,and acylcarnitines were measured in plasma samples. Results:The meldonium-induced depletion of L-carnitine and mitochondrial fatty acid oxidation was confirmed by reduced plasma levels of L-carnitine and acylcarnitines.Principal component analyses of the hepatic fatty acid composition revealed clustering dependent on meldonium and TTA.The meldonium-induced increase in hepatic triacylglycerol levels correlated negatively with estimated ac-tivities of elongases and was associated with higher estimated activities of delta-6 desaturase(D6D;C18:4n-3/C18:3n-3 and C18:3n-6/C18:2n-6),and increased circulating levels of C18:4n-3 and C18:3n-6(gamma-linolenic acid).TTA mitigated meldonium-induced triacylglycerol levels by 80％and attenu-ated the estimated D6D activities,and elongation of n-6 polyunsaturated fatty acids(PUFAs).TTA also attenuated the meldonium-mediated reduction of C24:1n-9(nervonic acid),possibly by stimulating Elovl5 and increased elongation of erucic acid(C22:1n-9)to nervonic acid.The hepatic levels of nervonic acid and the estimated activity of n-6 PUFA elongation correlated negatively with the hepatic tri-acylglycerol levels,while the estimated activities of D6D correlated positively. Conclusion:Circulating levels of gamma-linolenic acid,along with reduced estimated elongation of n-6 PUFAs and D6D desaturation activities,were associated with hepatic triacylglycerol levels.

Objective To explore the improving effect of eicosapentaenoic acid(EPA)on the skeletal muscle insulin resistance in obese rats by regulating the p38 MAPK signaling pathway.Methods Fifty male Wistar rats were randomly divided into the control group,model group,inhibitor group,EPA group and inhibi-tor+EPA group,10 cases in each group.The intervention lasted for 6 weeks.The inhibitor group was given 1 mg/kg p38 MAPK inhibitor SB203580 by gavage.The EPA group was given 70 mg/kg EPA by gavage,the in-hibitor+EPA group was given SB203580+EPA by gavage,and the model group and control group were given equal volume of saline.The levels of fasting blood-glucose,fasting serum insulin,glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)and malondialdehyde(MDA)in the skeletal muscles were deter-mined.The rat insulin resistance degree was evaluated by using the intraperitoneal glucose tolerance test(IPGTT)and insulin tolerance test(ITT).The protein and mRNA expression levels of phosphorylation p38 in the rat skeletal muscle tissues were detected by Western blot and qRT-PCR.Results Compared with the control group,the body weight,epididymal fat wet weight,fasting blood-glucose and insulin levels,IPGTT and ITT blood glucose levels,and MDA content in the model group were significantly increased,the GSH-Px and SOD activities were significantly decreased,and the relative expression levels of p-p38 protein and p38 mRNA expression in skeletal muscle tissues were significantly increased(P＜0.05).Compared with the model group,the body weight and epididymal fat wet weight in the EPA group and inhibitor+EPA group were sig-nificantly decreased,while the fasting blood-glucose,fasting serum insulin,IPGTT and ITT blood glucose lev-els and MDA contents in the inhibitor group and EPA group were significantly decreased,the activities of GSH-Px and SOD were significantly increased,and the relative expression level of p-p38 protein in skeletal muscle tissues was significantly decreased(P＜0.05).However,the expression of p38 mRNA in skeletal muscle tissues had no significant change(P＞0.05).Conclusion EPA alleviates the oxidative stress possibly by inhibiting p38 MAPK signaling pathway,thus improves the skeletal muscle insulin resistance of obese rats.

Background: High cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats. Methods: Seven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a highfat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies. Results: The obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer’s disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats. Conclusion The protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.

Overweight and obesity in Malaysia pose serious threats to health. Prevalence has escalated to alarming levels in recent decades despite a multitude of public health dietary messages geared towards obesity prevention and health promotion. Gaps between health messages, messengers, and the public must be identified and closed to effectively combat obesity and overweight. This review article aims to examine public health dietary messages, guidelines, and programmes for the prevention of obesity in Malaysia, and explore potential reasons for the continued rise in its prevalence. Public health dietary communication in Malaysia has progressed and improved substantially over the years. However, most messages have been designed for the general audience, with little consideration of differences in physical, social, cultural, and environmental backgrounds, and varying levels of comprehension. We offer several recommendations to increase the effectiveness of public health dietary messages in fighting the obesity epidemic, based on a cross-sectoral, place-based approach that recognise the complexity of the underlying causes of obesity.

Cardiomyocyte death is one of the major mechanisms contributing to the development of myocardial infarction (MI) and myocardial ischemia/reperfusion (MI/R) injury. Due to the limited regenerative ability of cardiomyocytes, understanding the mechanisms of cardiomyocyte death is necessary. Pyroptosis, one of the regulated programmed cell death pathways, has recently been shown to play important roles in MI and MI/R injury. Pyroptosis is activated by damage-associated molecular patterns (DAMPs) that are released from damaged myocardial cells and activate the formation of an apoptosis-associated speck-like protein containing a CARD (ASC) interacting with NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), resulting in caspase-1 cleavage which promotes the activation of Gasdermin D (GSDMD). This pathway is known as the canonical pathway. GSDMD has also been shown to be activated in a non-canonical pathway during MI and MI/R injury via caspase-4/5/11. Suppression of GSDMD has been shown to provide cardioprotection against MI and MI/R injury. Although the effects of MI or MI/R injury on pyroptosis have previously been discussed, knowledge concerning the roles of GSDMD in these settings remains limited. In this review, the evidence from in vitro, in vivo, and clinical studies focusing on cardiac GSDMD activation during MI and MI/R injury is comprehensively summarized and discussed. Implications from this review will help pave the way for a new therapeutic target in ischemic heart disease.