Some of the most interesting studies on palmitic acid, intake, phytochemistry.

Yang L, Guan G, Lei L, Lv Q, Liu S, Zhan X, Jiang Z, Gu X. Palmitic acid induces human osteoblast-like Saos-2 cell apoptosis via endoplasmic reticulum stress and autophagy. Cell Stress Chaperones. 2018 Nov;23(6):1283-1294. doi: 10.1007/s12192-018-0936-8.

Abstract. Palmitic acid (PA) is the most common saturated long-chain fatty acid in food that causes cell apoptosis. However, little is known about the molecular mechanisms of PA toxicity. In this study, we explore the effects of PA on proliferation and apoptosis in human osteoblast-like Saos-2 cells and uncover the signaling pathways involved in the process. Our study showed that endoplasmic reticulum (ER) stress and autophagy are involved in PA-induced Saos-2 cell apoptosis. We found that PA inhibited the viability of Saos-2 cells in a dose- and time-dependent manner. At the same time, PA induced the expression of ER stress marker genes (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)), altered autophagy-related gene expression (microtubule-associated protein 1 light chain 3 (LC3), ATG5, p62, and Beclin), promoted apoptosis-related gene expression (Caspase 3 and BAX), and affected autophagic flux. Inhibiting ER stress with 4-PBA diminished the PA-induced cell apoptosis, activated autophagy, and increased the expression of Caspase 3 and BAX. Inhibiting autophagy with 3-MA attenuated the PA and ER stress-induced cell apoptosis and the apoptosis-related gene expression (Caspase 3 and BAX), but seemed to have no obvious effects on ER stress, although the CHOP expression was downregulated. Taken together, our results suggest that PA-induced Saos-2 cell apoptosis is activated via ER stress and autophagy, and the activation of autophagy depends on the ER stress during this process.

Yang L, Wei J, Sheng F, Li P. Attenuation of Palmitic Acid-Induced Lipotoxicity by Chlorogenic Acid through Activation of SIRT1 in Hepatocytes. Mol Nutr Food Res. 2019 Jul;63(14):e1801432. doi: 10.1002/mnfr.201801432. 

Abstract. Scope: Saturated free fatty acids (FFAs) induce hepatocyte lipotoxicity, wherein oxidative stress-associated mitochondrial dysfunction is mechanistically involved. Chlorogenic acid (CGA), a potent antioxidant and anti-inflammatory compound, protects against high-fat-diet-induced oxidative stress and mitochondrial dysfunction in liver. This study investigates whether CGA protects against FFA-induced hepatocyte lipotoxicity via the regulation of mitochondrial fission/fusion and elucidates its underlying mechanisms....© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
 

Flores-León M, Pérez-Domínguez M, González-Barrios R, Arias C. Palmitic Acid-Induced NAD+ Depletion is Associated with the Reduced Function of SIRT1 and Increased Expression of BACE1 in Hippocampal Neurons. Neurochem Res. 2019 Jul;44(7):1745-1754. doi: 10.1007/s11064-019-02810-8. 

Abstract. Increased levels of circulating fatty acids, such as palmitic acid (PA), are associated with the development of obesity, insulin resistance, type-2 diabetes and metabolic syndrome. Furthermore, these diseases are linked to an increased risk of cancer, cardiovascular diseases, mild cognitive impairment and even Alzheimer's disease (AD). However, the precise actions of elevated PA levels on neurons and their association with neuronal metabolic disruption that leads to the expression of pathological markers of AD, such as the overproduction and accumulation of the amyloid-β peptide, represent an area of intense investigation. A possible molecular mechanism involved in the effects of PA may be through dysfunction of the NAD+ sensor enzyme, SIRT1. Therefore, the aim of the present study was to analyze the relationship between the effects of PA metabolism on the function of SIRT1 and the upregulation of BACE1 in cultured hippocampal neurons. PA reduced the total amount of NAD+ in neurons that caused an increase in p65 K310 acetylation due to inhibition of SIRT1 activity and low protein content. Furthermore, BACE1 protein and its activity were increased, and BACE1 was relocated in neurites after PA exposure.

Ben-Dror K, Birk R. Oleic acid ameliorates palmitic acid-induced ER stress and inflammation markers in naive and cerulein-treated exocrine pancreas cells. Biosci Rep. 2019 May 14;39(5):BSR20190054. doi: 10.1042/BSR20190054. 

Abstract. Dietary fat overload (typical to obesity) increases the risk of pancreatic pathologies through mechanisms yet to be defined. We previously showed that saturated dietary fat induces pancreatic acinar lipotoxicity and cellular stress. The endoplasmic reticulum (ER) of exocrine pancreas cells is highly developed and thus predisposed to stress. We studied the combination of saturated and unsaturated FAs in metabolic and pancreatitis like cerulein (CER)-induced stress states on cellular ER stress.Exocrine pancreas AR42J and rat primary exocrine acinar cells underwent acute (24 h) challenge with different FAs (saturated, monounsaturated) at different concentrations (250 and 500 µM) and in combination with acute CER-induced stress, and were analyzed for fat accumulation, ER stress unfolded protein response (UPR) and immune and enzyme markers....© 2019 The Author(s).

Guan G, Lei L, Lv Q, Gong Y, Yang L. Curcumin attenuates palmitic acid-induced cell apoptosis by inhibiting endoplasmic reticulum stress in H9C2 cardiomyocytes. Hum Exp Toxicol. 2019 Jun;38(6):655-664. doi: 10.1177/0960327119836222. 

Abstract. Diabetic cardiomyopathy is mediated by multiple molecular mechanisms including endoplasmic reticulum (ER) stress. Curcumin, a phenolic compound, has cytoprotective properties, but its potential protective action against diabetic cardiomyopathy and the related molecular mechanisms are not fully elucidated. In this study, we evaluated the effects of curcumin on cell viability and apoptosis in palmitic acid (PA)-treated H9C2 cardiomyocytes and investigated the signaling pathways involved. Treatment with PA reduced cell viability, induced apoptosis, enhanced apoptosis-related protein expression (Caspase 3 and BCL-2 associated X protein (BAX)), and activated ER stress marker protein expression (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Curcumin attenuated PA-induced reduction in cell viability and activation of apoptosis, Caspase 3 activity, BAX, CHOP, and GRP78 expression. 4-Phenylbutyric acid (4-PBA) attenuated the PA-induced effects on cell viability and apoptosis, similar to curcumin. Both curcumin and 4-PBA also attenuated PA-induced increase in ER stress protein (CHOP and GRP78) expression. Curcumin also protected against cytotoxicity, apoptosis, and ER stress induced by thapsigargin. These findings indicate that PA triggers apoptosis in H9C2 cells via ER stress pathways and curcumin protects against this phenomenon.

Ramírez D, Saba J, Turati J, Carniglia L, Imsen M, Mohn C, Scimonelli T, Durand D, Caruso C, Lasaga M. NDP-MSH reduces oxidative damage induced by palmitic acid in primary astrocytes. J Neuroendocrinol. 2019 Feb;31(2):e12673. doi: 10.1111/jne.12673.

Abstract. Recent findings relate obesity to inflammation in key hypothalamic areas for body weight control. Hypothalamic inflammation has also been related to oxidative stress. Palmitic acid (PA) is the most abundant free fatty acid found in food, and in vitro studies indicate that it triggers a pro-inflammatory response in the brain. Melanocortins are neuropeptides with proven anti-inflammatory and neuroprotective action mediated by melanocortin receptor 4 (MC4R), but little is known about the effect of melanocortins on oxidative stress. The aim of this study was to investigate whether melanocortins could alleviate oxidative stress induced by a high fat diet (HFD) model....© 2019 British Society for Neuroendocrinology.

Choi CW, Kim Y, Kim JE, Seo EY, Zouboulis CC, Kang JS, Youn SW, Chung JH. Enhancement of lipid content and inflammatory cytokine secretion in SZ95 sebocytes by palmitic acid suggests a potential link between free fatty acids and acne aggravation. Exp Dermatol. 2019 Feb;28(2):207-210. doi: 10.1111/exd.13855.

Abstract. A relationship between acne and free fatty acids (FFAs) has been suggested recently. However, the effects of FFAs on sebaceous glands are still largely unknown. At the same time, the role of FFAs during chronic inflammation is well established. Considering that FFAs are also a major component of sebum, it is likely that changes in FFA affect both the synthesis of sebum and the inflammatory response in sebaceous glands. In this study, we examined a hypothesis that FFAs increase the production of sebum and induce inflammation in the sebaceous glands. ...© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Suzuki E, Matsuda T, Kawamoto T, Takahashi H, Mieda Y, Matsuura Y, Takai T, Kanno A, Koyanagi-Kimura M, Asahara SI, Inoue H, Ogawa W, Kido Y. Docosahexaenoic Acid Reduces Palmitic Acid-Induced Endoplasmic Reticulum Stress in Pancreatic Β Cells. Kobe J Med Sci. 2018 Sep 11;64(2):E43-E55. 

Abstract. Endoplasmic reticulum (ER) stress leads to peripheral insulin resistance and the progression of pancreatic beta cell failure in type 2 diabetes. Although ER stress plays an important role in the pathogenesis of diabetes, it is indispensable for cellular activity. Therefore, when assessing the pathological significance of ER stress, it is important to monitor and quantify ER stress levels. Here, we have established a novel system to monitor ER stress levels quickly and sensitively, and using this method, we have clarified the effect of differences in glucose concentration and various fatty acids on the ER of pancreatic β cells. First, we developed a cell system that secretes Gaussia luciferase in culture medium depending on the activation of the GRP78 promoter. This system could sensitively monitor ER stress levels that could not be detected with real-time RT-PCR and immunoblotting. This system revealed that hyperglycemia does not induce unfolded protein response (UPR) in a short period of time in MIN6 cells, a mouse pancreatic β cell line. Physiological concentrations of palmitic acid, a saturated fatty acid, induced ER stress quickly, while physiological concentrations of oleic acid, an unsaturated fatty acid, did not. Docosahexaenoic acid, an n-3 unsaturated fatty acid, inhibited palmitic acid-induced ER stress. In this study, we have established a system that can sensitively detect ER stress levels of living cells in a short period of time. This system can be used to monitor the state of the ER in living cells and lead to the investigation of the significance of physiological or pathological ER stress levels.

Cansanção K, Silva Monteiro L, Carvalho Leite N, Dávalos A, Tavares do Carmo MDG, Arantes Ferreira Peres W. Advanced Liver Fibrosis Is Independently Associated with Palmitic Acid and Insulin Levels in Patients with Non-Alcoholic Fatty Liver Disease. Nutrients. 2018 Oct 29;10(11):1586. doi: 10.3390/nu10111586. 

Abstract. Changes in lipid metabolism occur during the development and progression non-alcoholic fatty liver disease (NAFLD). However, the fatty acid (FA) profile in red blood cells (RBC) from patients with liver fibrosis remains unexplored. Thus, the goal of this study was to evaluate the fatty acid profile in RBC, dietary lipid intake and insulin resistance indicators in patients with NAFLD, according to the degree of hepatic fibrosis. Using elastography, patients were classified with (n = 52) and without (n = 37) advanced liver fibrosis. The fatty acid profile in RBC was analyzed using gas chromatography and the lipid intake was evaluated through a 24-h dietary recall. Subjects with advanced liver fibrosis had higher levels of palmitic, stearic and oleic acid and total monounsaturated fatty acid (MUFA) and insulin (p < 0.05), and lower levels of elongase very long chain fatty acids protein-6 and the delta-5-desaturase enzymatic activity (p < 0.05). These results suggest a lack of regulation of enzymes related to FA metabolism in patients with advanced fibrosis.