Protection Strategies Against Palmitic Acid-Induced Lipotoxicity in Metabolic Syndrome and Related Diseases

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 788 - 788

Published: Jan. 18, 2025

Diets rich in carbohydrate and saturated fat contents, when combined with a sedentary lifestyle, contribute to the development of obesity metabolic syndrome (MetS), which subsequently increase palmitic acid (PA) levels. At high concentrations, PA induces lipotoxicity through several mechanisms involving endoplasmic reticulum (ER) stress, mitochondrial dysfunction, inflammation cell death. Nevertheless, there are endogenous strategies mitigate PA-induced its unsaturation elongation channeling storage lipid droplets (LDs), plays crucial role sequestering oxidized lipids, thereby reducing oxidative damage membranes. While extended exposure promotes reactive oxygen species (ROS) generation leading damage, acute ß-cells increases glucose-stimulated insulin secretion (GSIS), activation free fatty receptors (FFARs). Subsequently, FFARs by exogenous agonists has been suggested as potential therapeutic strategy prevent ß cells. Moreover, some acids, including oleic acid, can counteract negative impact on cellular health, suggesting complex interaction between different dietary fats outcomes. Therefore, challenge is peroxidation unsaturated acids utilization natural antioxidants. This complexity indicates necessity for further research into function diverse pathological conditions find main target against lipotoxicity. The aim this review is, therefore, examine recent data regarding mechanism underlying order identify that promote protection lipotoxicity, dysfunction apoptosis MetS obesity.

Language: Английский

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Diet-derived and diet-related endogenously produced palmitic acid: Effects on metabolic regulation and cardiovascular disease risk

Journal of clinical lipidology, Journal Year: 2023, Volume and Issue: 17(5), P. 577 - 586

Published: July 28, 2023

Palmitic acid is the predominant dietary saturated fatty (SFA) in US diet. Plasma palmitic derived from fat and also endogenously de novo lipogenesis (DNL) lipolysis. DNL affected by excess energy intake resulting overweight obesity, macronutrient profile of A low-fat diet (higher carbohydrate and/or protein) promotes synthesis adipocytes liver. high-fat another source that taken up adipose tissue, liver, heart skeletal muscle via lipolytic mechanisms. Moreover, overweight/obesity accompanying insulin resistance increase non-esterified (NEFA) production. may affect cardiovascular disease (CVD) risk mechanisms beyond increasing LDL-C, notably ceramides possibly through branched esters hydroxy acids (FAHFAs) acid. Ceramides are positively associated with incident CVD, whereas role FAHFAs uncertain. Given new evidence about regulation metabolism there interest learning more how modulates circulating concentrations and, hence, potentially CVD risk. This important because heightened low (carbohydrate controlled) high (low-fat) diets coupled ongoing epidemic, all which can plasma levels different Consequently, biochemistry, trafficking its metabolites will inform future guidance to further lower burden CVD.

Language: Английский

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Low levels and partial exposure to palmitic acid improves mitochondrial function and the oxidative status of cultured cardiomyoblasts

Toxicology Reports, Journal Year: 2024, Volume and Issue: 12, P. 234 - 243

Published: Feb. 2, 2024

Lipid overload or metabolic stress has gained popularity in research that explore pathological mechanisms may drive enhanced oxidative myocardial damage. Here, H9c2 cardiomyoblasts were exposed to various doses of palmitic acid (0.06 1 mM) for either 4 24 hours study its potential physiological response cardiac cells. Briefly, assays performed included activity, cholesterol content, mitochondrial respiration, and prominent markers stress, as well determining changes potential, production reactive oxygen species, intracellular antioxidant levels like glutathione, glutathione peroxidase superoxide dismutase. Cellular damage was assessed through probing with fluorescent stains, annexin V propidium iodide. Our results indicated prolonged exposure (24-hours) ≥ 0.5 mM significantly impaired status, leading membrane increased ROS production. While dose appeared induce damage, likely because capacity increase content/ lipid peroxidation severely suppressing antioxidants. Interestingly, short-term (4-hours) acid, especially lower (≤ 0.25 mM), could improve function protect against induced Potentially suggesting that, depending on the consumed duration exposure, consumption saturated fatty acids such can differently affect myocardium. However, these are still preliminary, vivo is required understand significance maintaining antioxidants by overload.

Language: Английский

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Saturated fats, dairy foods and cardiovascular health: No longer a curious paradox?

Nutrition Bulletin, Journal Year: 2022, Volume and Issue: 47(4), P. 407 - 422

Published: Oct. 26, 2022

Cardiovascular diseases (CVDs) are a major cause of death and morbidity in many parts the world, dietary guidelines limit intake saturated fatty acids (SFA) as they regarded an important risk factor for CVDs due to their association with increased blood cholesterol. Dairy foods often contributor SFA, since contain restrictions on SFA intake, this can lead moderation dairy food despite meta-analyses generally showing have neutral or negative CVDs. Many prospective studies randomised controlled trials do not support simple positive between atherosclerotic CVD its components although some early had number methodological weakness. Studies that included cholesterol data broadly relationship low-density lipoprotein (LDL-C) but without resulting, LDL being causal CVD. These suggest LDL-C alone is consistently good predictor risk, perhaps particularly relation consumption non-dairy also shown reduction was reflected reduced risk. This narrative review examines reasons these findings. Overall, seem warranted, there remains need further understand different types chronic diseases, type 2 diabetes.

Language: Английский

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Exploring the impacts of ketogenic diet on reversible hepatic steatosis: initial analysis in male mice

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: March 21, 2024

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic disease. Ketogenic diet (KD), a with very low intake in carbohydrates, gained popularity as weight-loss approach. However, mice models, it has been reported that an excess exposition of dietary fat induces hepatic insulin resistance and steatosis. data published inconsistent. Herein, we investigated mouse model, metabolic effects KD its contribution to pathogenesis NALFD. Mice were exposed or CHOW for 12 weeks while third group was also then switched 4 determine if can rescue phenotype. We evaluated treatments on distribution, glucose, homeostasis well fed developed glucose intolerance but not accompanied by increase inflammation. KD-fed showed accumulation white adipose tissue liver. This effect could be explained uptake no changes catabolism leading MAFLD. Interestingly, able phenotype switching diet. Our studies demonstrate even develop steatosis after KD, they do more importantly, reversed from CHOW.

Language: Английский

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Functional consequences of brain exposure to saturated fatty acids: From energy metabolism and insulin resistance to neuronal damage

Endocrinology Diabetes & Metabolism, Journal Year: 2022, Volume and Issue: 6(1)

Published: Nov. 2, 2022

Abstract Introduction Saturated fatty acids (FAs) are the main component of high‐fat diets (HFDs), and high consumption has been associated with development insulin resistance, endoplasmic reticulum stress mitochondrial dysfunction in neuronal cells. In particular, reduction signaling seems to underlie cognitive impairments considered a risk factor for Alzheimer's disease (AD). Methods This review summarized critically analyzed research that impacted field saturated FA metabolism neurons. Results We reviewed mechanisms free transport from systemic circulation brain how they impact metabolism. Finally, we focused on molecular physiopathological consequences exposure most abundant HFD, palmitic acid (PA). Conclusion Understanding lead metabolic alterations neurons induced by FAs could help develop several strategies prevention treatment impairment syndrome, or type II diabetes.

Language: Английский

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Differential Lipid Accumulation on HepG2 Cells Triggered by Palmitic and Linoleic Fatty Acids Exposure

Molecules, Journal Year: 2023, Volume and Issue: 28(5), P. 2367 - 2367

Published: March 4, 2023

Lipid metabolism pathways such as β-oxidation, lipolysis and, lipogenesis, are mainly associated with normal liver function. However, steatosis is a growing pathology caused by the accumulation of lipids in hepatic cells due to increased dysregulated lipid metabolism, and/or reduced lipolysis. Accordingly, this investigation hypothesizes selective vitro palmitic and linoleic fatty acids on hepatocytes. After assessing metabolic inhibition, apoptotic effect, reactive oxygen species (ROS) generation (LA) (PA) acids, HepG2 were exposed different ratios LA PA study using lipophilic dye Oil Red O. Lipidomic studies also carried out after isolation. Results revealed that was highly accumulated induced ROS production when compared PA. profile modifications observed LA:PA 1:1 (v/v) exposure, which led four-fold increase triglycerides (TGs) (mainly acid-containing species), well cholesterol polyunsaturated (PUFA) content control cells. The present work highlights importance balancing both concentrations maintain levels free (FFAs), cholesterol, TGs minimize some effects (i.e., apoptosis, accumulation) these acids.

Language: Английский

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Hypertrophy and ER Stress Induced by Palmitate Are Counteracted by Mango Peel and Seed Extracts in 3T3-L1 Adipocytes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5419 - 5419

Published: March 12, 2023

A diet rich in saturated fatty acids (FAs) has been correlated with metabolic dysfunction and ROS increase the adipose tissue of obese subjects. Thus, reducing hypertrophy oxidative stress can represent a strategy to counteract obesity obesity-related diseases. In this context, present study showed how peel seed extracts mango (Mangifera indica L.) reduced lipotoxicity induced by high doses sodium palmitate (PA) differentiated 3T3-L1 adipocytes. Mango (MPE) (MSE) significantly lowered PA-induced fat accumulation lipid droplet (LDs) triacylglycerol (TAGs) content We that MPE MSE activated hormone-sensitive lipase, key enzyme TAG degradation. addition, down-regulated adipogenic transcription factor PPARγ as well AMPK consequent inhibition acetyl-CoA-carboxylase (ACC). Notably, PA increased endoplasmic reticulum (ER) markers GRP78, PERK CHOP, enhanced reactive oxygen species (ROS) These effects were accompanied reduction cell viability induction apoptosis. Interestingly, counteracted ER production. level anti-oxidant Nrf2 its targets MnSOD HO-1. Collectively, these results suggest intake extract-enriched foods association correct lifestyle could exert beneficial obesity.

Language: Английский

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Nutritional regulation of hepatic de novo lipogenesis in humans

Current Opinion in Clinical Nutrition & Metabolic Care, Journal Year: 2023, Volume and Issue: 26(2), P. 65 - 71

Published: Jan. 3, 2023

Purpose of review De novo lipogenesis (DNL) is a metabolic process occurring mainly within the liver, in humans. Insulin primary signal for promoting DNL; thus, nutritional state key determinant upregulation pathway. However, effects dietary macronutrient composition on hepatic DNL remain unclear. Nor it clear if nutrition-induced increase results accumulation intra-hepatic triglyceride (IHTG); mechanism often proposed pathological IHTG. Here, we latest evidence surrounding regulation DNL. Recent findings The role carbohydrate intake has been well studied, with only limited data fats and proteins. Overall, increasing typically an DNL, fructose being more lipogenic than glucose. For fat, appears that increased n-3 polyunsaturated fatty acids downregulates whilst, contrast, protein may upregulate Summary Although upregulated high-carbohydrate or mixed-macronutrient meal consumption, fat Additionally, different phenotypes (including sex, age, ethnicity, menopause status) combination diets (enriched macronutrients) requires elucidation.

Language: Английский

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Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds

International Journal of Analytical Chemistry, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 20

Published: Sept. 22, 2023

Secondary metabolites are hidden gems in mushrooms. Understanding these secondary metabolites' biological and pharmacological effects can be aided by identifying them. The purpose of this work was to profile the mycochemical components extracts Auricularia auricula judae, Microporus xanthopus, Termitomyces umkowaani, Trametes elegans, versicolor comprehend their capabilities. Mushroom samples were collected from Kenya's Arabuko-Sokoke Kakamega National Reserved Forests identified using morphological molecular techniques. Chloroform, 70% ethanol, hot water solvents used extract components. Gas chromatography mass spectrometry (GC-MS) analyze chloroform, all species examined. A total 51 compounds isolated classified as carboxylic acids, esters, phenols, fatty alcohol, epoxides, aldehydes, isoprenoid lipids, steroids. Tetracosamethyl-cyclododecasiloxane (18.90%), oleic acid (72.90%), phenol, 2, 6-bis (1, 1-dimethylethyl)-4-methyl-, methylcarbamate (26.56%) found high concentrations A. auricular M. T. versicolor, respectively. Fatty acids make up majority elegans chloroform umkowaani ethanol extract, Particularly, play crucial roles anti-inflammatory, hypocholesterolemic, anticancer, antibiofilm formation activities. These bioactive elements indicate that five wild mushrooms may reliable sources for therapeutic development. Therefore, additional research is required usefulness chemicals many functional areas improve present understanding macrofungi.

Language: Английский

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