The effect of FFAR1 on pioglitazone-mediated attenuation of palmitic acid-induced oxidative stress and apoptosis in βTC6 cells

Shen, Xiaodong; Yang, Liyong; Yan, Sunjie; Wei, Wei; Liang, Liyu; Zheng, Hao; Cai, Xiuhui

doi:10.1016/j.metabol.2013.11.003

Cited by 23 publications

(33 citation statements)

References 29 publications

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“…Correlatively, increased 5-HIAA in the amygdala is associated with anxiety-like behavior in mice [69]. Recently it has been noted that palmitic acid can be lipotoxic to cells, inducing accumulation of reactive oxygen species (ROS) [70], leading to endoplasmic reticulum (ER) stress [71] and apoptosis [72]. Additionally, ER stress has been implicated in the FFA-induced complications of obesity [73,74].…”

Section: Discussionmentioning

confidence: 99%

The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice

Moon¹,

Joesting²,

Lawson³

et al. 2014

Metabolism

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Objectives Excess fat in the diet can impact neuropsychiatric functions by negatively affecting cognition, mood and anxiety. We sought to show that the free fatty acid (FFA), palmitic acid, can cause adverse biobehaviors in mice that lasts beyond an acute elevation in plasma FFAs. Methods Mice were administered palmitic acid or vehicle as a single intraperitoneal (IP) injection. Biobehaviors were profiled 2 and 24 hrs after palmitic acid treatment. Quantification of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their major metabolites was performed in cortex, hippocampus and amygdala. FFA concentration was determined in plasma. Relative fold change in mRNA expression of unfolded protein response (UPR)-associated genes was determined in brain regions. Results In a dose-dependent fashion, palmitic acid rapidly reduced mouse locomotor activity by a mechanism that did not rely on TLR4, MyD88, IL-1, IL-6 or TNFα but was dependent on fatty acid chain length. Twenty-four hrs after palmitic acid administration mice exhibited anxiety-like behavior without impairment in locomotion, food intake, depressive-like behavior or spatial memory. Additionally, the serotonin metabolite 5-HIAA was increased by 33% in the amygdala 24 hrs after palmitic acid treatment. Conclusions Palmitic acid induces anxiety-like behavior in mice while increasing amygdala-based serotonin metabolism. These effects occur at a time point when plasma FFA levels are no longer elevated.

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Section: Discussionmentioning

confidence: 99%

The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice

Moon¹,

Joesting²,

Lawson³

et al. 2014

Metabolism

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“…Furthermore, palmitate exposure may induce apoptosis in isolated islets from humans [43,48], possibly through its receptor cell death-inducing DFF45-like effector b (Cideb) [48]. Oxidative stress is another negative effect under palmitate exposure, accompanied with apoptosis in βTC6 cells (a glucose-sensitive mouse β pancreatic cell line) through activating free fatty acid receptor 1 (FFAR1) [49]. Therefore, fructose-induced FFA production (especially palmitate) may disturb insulin secretion by disturbing the function of pancreatic islet β cells.…”

Section: Direct Dangerous Factors Under High Fructose Consumptionmentioning

confidence: 99%

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

2017

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High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

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“…Fluorescein-12-dUTP incorporation results in localized green fluorescence within the nucleus of apoptotic cells only. The detection of rat islets β-cell apoptosis by flow cytometric analysis was referred to our previous methods (Shen et al, 2014).…”

Section: Apoptosis Analysis By Tunel Analysis and Flow Cytometrymentioning

confidence: 99%

“…Our previous studies have shown that PIO can reduce β-cell apoptosis (Shen et al, 2014). Recent studies have reported that PIO might exert an anti-inflammatory response by decreasing the expression of TLR4 in renal tissue, and regulating the balance between proinflammatory and anti-inflammatory signals (Yu et al, 2014).…”

Section: Introductionmentioning

confidence: 96%