Melatonin protects HT-22 cells against palmitic acid-induced glucolipid metabolic dysfunction and cell injuries: Involved in the regulation of synaptic plasticity and circadian rhythms

Gao, Xinran; Sun, Huaizhi; Hao, Shengwei; Sun, Huimin; Ge, Jinfang

doi:10.1016/j.bcp.2023.115846

Cited by 4 publications

(2 citation statements)

References 70 publications

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“…Moreover, it has been reported that MLT has a potential effect on diabetes and its complications via regulating insulin secretion [ 26 ]. Consistently, in our previous study, we found that MLT can improve both the metabolic dysfunction and impaired learning and memory in T2DM mice induced by a combination of a high-fat diet and STZ intraperitoneal injection, the mechanism of which might be involved with the regulation of circadian rhythm and neuroinflammation [ 27 ]. These results suggest that MLT might be a potential therapeutic agent for cognitive impairment caused by T2DM [ 28 ].…”

Section: Introductionsupporting

confidence: 85%

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM

He,

Yu,

Chen

et al. 2024

Journal of Diabetes Research

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Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients.Methods: One hundred twenty‐six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C‐reactive protein (CRP), Interleukin 6 (IL‐6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function‐Adult Version (BRIEF‐A) and the Epidemiological Research Center Depression Scale (CES‐D), respectively.Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF‐A and CES‐D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF‐A and CES‐D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients.Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM‐associated executive impairment and depression status.

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Section: Introductionsupporting

confidence: 85%

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM

He,

Yu,

Chen

et al. 2024

Journal of Diabetes Research

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“…PA is a substrate for fatty acid oxidation and is crucial for regulating energy homeostasis. 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.…”

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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Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice

Gao,

Sun,

Wei

et al. 2024

Phytomedicine

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Melatonin protects HT-22 cells against palmitic acid-induced glucolipid metabolic dysfunction and cell injuries: Involved in the regulation of synaptic plasticity and circadian rhythms

Cited by 4 publications

References 70 publications

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM

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

Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice

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