Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF‐α and caspase‐3 in palmitic acid‐induced lipotoxicity in myoblasts

Mansuri, Mohammad Lukman; Sharma, Garima; Parihar, Priyanka; Dube, Kirti Tiwari; Sharma, Tejasweta; Parihar, Arti; Parihar, Mordhwaj S.

doi:10.1002/jbt.22744

Cited by 5 publications

(5 citation statements)

References 71 publications

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“…However, while most studies have detected increased oxidative stress after PA treatment in other cell types [189,190] as the most likely cause of DNA damage the study from Ishaq and coworkers [5] did not find an increase in mitochondrial superoxide after PA treatment suggesting alternative mechanisms for the induction of DNA damage. There are some alternative pathways that could explain the occurrence of DNA damage without measurable mitochondrial superoxide levels.…”

Section: Palmitic Acid As An Inducer Of Senescence In Human Adipocyte...mentioning

confidence: 88%

“…However, Ishaq and co-authors only found trends for increase of inflammatory markers after PA treatment in subcutaneous adipocytes in vitro [5]. Previous studies had demonstrated that increased contact of adipocytes with PA promoted direct detrimental intracellular effects [189][190][191]. There are two main pathways for PA-induced cellular stress: endoplasmic reticulum (ER) stress and mitochondrial ROS generation.…”

Section: Co-treatment Of Oa and Pa In Donor-derived Isogenic Subcutan...mentioning

confidence: 99%

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Senescence and DNA Damage in Adipocytes and Fat Tissues and Its Potential Amelioration through Nutritional Interventions

Ishaq¹,

Saretzki²

2022

RPN

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Accumulating evidence demonstrates that senescence and the associated inflammatory phenotype (SASP) also occur in post-mitotic cells such as mature adipocytes. Visceral adipose tissue in humans is susceptible to inflammation due to nutritional imbalance and ageing. However, while adipose tissue has been well researched in the context of obesity, senescence of differentiated adipocytes has not been investigated thoroughly. Our group recently demonstrated that ageing and normal ad libitum (AL) nutrition in mice resulted in increased adipocyte size, DNA damage, p16INK4a expression and inflammation in visceral adipose tissue while some of these senescence markers could be alleviated by dietary restriction (DR). Moreover, another dietary restriction study described a “metabolic memory” as protection against AL-induced senescence after shifting mice from DR back to AL nutrition. Other recent DR studies on mice of different ages analysed the transcriptional profile of adipose tissue and described a metabolic memory for AL at high age. Finally, our group modelled nutritional imbalance in vitro through treatment of primary human subcutaneous and omental adipocytes with the saturated fatty acid (FA) palmitic acid (PA). This resulted in a significant increase in DNA damage as well as p16INK4a levels correlating with enhanced intracellular lipid accumulation. In contrast, DNA damage could be prevented with the unsaturated FA oleic acid (OA). With olive oil being an important part of the Mediterranean diet another study found also other oils such as argan oil to have similar effects of preventing DNA damage in vivo and in vitro. This review is focused on senescence, DNA damage and inflammation in WAT and adipocytes including nutritional interventions in vivo and in vitro. It also gives some basic background on these topics. However, it is not a systematic review but aims to highlight recent developments and nutritional interventions in the areas of senescence and DNA damage related to adipocyte tissues and cells.

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Section: Palmitic Acid As An Inducer Of Senescence In Human Adipocyte...mentioning

confidence: 88%

Section: Co-treatment Of Oa and Pa In Donor-derived Isogenic Subcutan...mentioning

confidence: 99%

Senescence and DNA Damage in Adipocytes and Fat Tissues and Its Potential Amelioration through Nutritional Interventions

Ishaq¹,

Saretzki²

2022

RPN

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show abstract

Section: Palmitic Acid As An Inducer Of Senescence In Human Adipocyte...mentioning

confidence: 99%

Section: Co-treatment Of Oa and Pa In Donor-derived Isogenic Subcutan...mentioning

confidence: 99%

Untitled

2022

RPN

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Accumulating evidence demonstrates that senescence and the associated inflammatory phenotype (SASP) also occur in post-mitotic cells such as mature adipocytes. Visceral adipose tissue in humans is susceptible to inflammation due to nutritional imbalance and ageing. However, while adipose tissue has been well researched in the context of obesity, senescence of differentiated adipocytes has not been investigated thoroughly. Our group recently demonstrated that ageing and normal ad libitum (AL) nutrition in mice resulted in increased adipocyte size, DNA damage, p16 INK4a expression and inflammation in visceral adipose tissue while some of these senescence markers could be alleviated by dietary restriction (DR). Moreover, another dietary restriction study described a "metabolic memory" as protection against AL-induced senescence after shifting mice from DR back to AL nutrition. Other recent DR studies on mice of different ages analysed the transcriptional profile of adipose tissue and described a metabolic memory for AL at high age. Finally, our group modelled nutritional imbalance in vitro through treatment of primary human subcutaneous and omental adipocytes with the saturated fatty acid (FA) palmitic acid (PA). This resulted in a significant increase in DNA damage as well as p16 INK4a levels correlating with enhanced intracellular lipid accumulation. In contrast, DNA damage could be prevented with the unsaturated FA oleic acid

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“…As a driver of lipotoxicity, it has been shown that excessive PA mediated increase in cellular reactive oxygen species (ROS) activates cell apoptosis in different cell types, including HepG2 cells [3], porcine intestinal epithelial cells [4] and HT-22 cells [5]. Significantly, in higher energy requirements myocytes, excessive PA also caused a decrease in mitochondrial membrane potential (MMP) [6,7], mitochondrial respiratory capacity [8,9], and destroyed mitochondrial DNA and morphology by decreasing the protein expression of mitochondrial fusion, fission, biogenesis, which in turn leads to cell death. Thus, we hypothesized that PA may could also induce a mitochondrial dysfunction in BEECs, which in turn activate the apoptotic pathway.…”

Section: Introductionmentioning

confidence: 99%

Melatonin alleviates palmitic acid–induced mitochondrial dysfunction by decreasing oxidative stress and enhancing autophagy combined in bovine endometrial epithelial cells

Wang,

Zhu,

Zhao

et al. 2024

Preprint

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Background: Negative energy balance (NEB) typically occurs in dairy cows after delivery, with those in high yielding being more likely to experience significant NEB. Such metabolic imbalance could cause ketosis, which is often accompanied by a decline in reproductive performance, but the molecular mechanism has not been fully elucidated. During excessive NEB, the body fat is extensively broken down, resulting in abnormal accumulation of non-esterified fatty acids (NEFA), represented by palmitic acid (PA), within the uterus. Such an abnormal accumulation has the potential to damage bovine endometrial epithelial cells (BEECs), while the molecular mechanisms underlying its involvement in the PA-induced injury of BEECs is poorly understood. Melatonin (MT) is recognized for its regulatory role in maintaining the homeostasis of mitochondrial reactive oxygen species (mitoROS). However, less is known about whether MT could ameliorate the damage of PA on BEECs and its molecular mechanism. Results: Our results demonstrated that 0.2 mM PA stress increased the level of cellular and mitochondrial oxidative stress. Further, we observed mitochondrial dysfunction, including an abnormal incidence of mitochondrial structure and respiratory function, reduction in mitochondrial membrane potential and mitochondrial copy number, which in turn induced apoptosis. Notably, we also found an upregulation of autophagy protein (PINK, Parkin, LC3B et al), however, the P62 protein was also increased. As we expected, 100uM MT pre-treatment attenuated PA-induced mitochondrial ROS and restored mitochondrial respiratory function. Meanwhile, pre-treated MT reversed the upregulation of P62 induced by PA and activate the AMPK-mTOR-Beclin-1 pathway, contributing to increase of autophagy and decline apoptosis. Conclusions: These findings indicate that PA could induce mitochondrial dysfunction and also enhance autophagy in BEECs. In addition, MT is hypothesized to not only reduce mitochondrial oxidative stress but also facilitate the clearance of damaged mitochondria through the regulation of autophagy pathways, thereby safeguarding the mitochondrial pool and promoting cellular viability. Our study helps better understand the molecular mechanism involved in excessive NEB's impact on the fertility outcomes of high yielding dairy cows.

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Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF‐α and caspase‐3 in palmitic acid‐induced lipotoxicity in myoblasts

Cited by 5 publications

References 71 publications

Senescence and DNA Damage in Adipocytes and Fat Tissues and Its Potential Amelioration through Nutritional Interventions

Senescence and DNA Damage in Adipocytes and Fat Tissues and Its Potential Amelioration through Nutritional Interventions

Untitled

Melatonin alleviates palmitic acid–induced mitochondrial dysfunction by decreasing oxidative stress and enhancing autophagy combined in bovine endometrial epithelial cells

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