DHA reduces hypothalamic inflammation and improves central leptin signaling in mice

Cheng, Licai; Hu, Tao; Shi, Hongli; Chen, Xi; Wang, Hongqin; Zheng, Kuiyang; Huang, Xu‐Feng; Yu, Yinghua

doi:10.1016/j.lfs.2020.118036

Cited by 18 publications

(9 citation statements)

References 62 publications

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“…Whereas SFAs are detrimental to neuropeptide levels, impair insulin signaling, and promote inflammation, MUFAs and PUFAs have opposing or neutral effects. 9,10,27,34,35 Our laboratory has previously established that oleate is capable of preventing and alleviating the effects of palmitate on Npy, Pomc, glucoseregulated protein 78 (Grp78) and interleukin-6 (Il-6) genes in the mHypoE-46 cells when these FAs are cotreated. 9,27 DHA cotreatment with palmitate was additionally shown to blunt the effects of palmitate on the circadian transcription factor Bmal1.…”

Section: Unsaturated Fatty Acids Oleate and Dha Prevent Palmitate-med...mentioning

confidence: 99%

Palmitate alters miR‐2137 and miR‐503‐5p to induce orexigenic Npy in hypothalamic neuronal cell models: Rescue by oleate and docosahexaenoic acid

McIlwraith

Belsham

2023

J Neuroendocrinology

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MicroRNAs (miRNAs) are short noncoding RNA implicated in the pathogenesis of obesity. One cause of obesity is excess exposure to the saturated fatty acid palmitate that can alter miRNA levels in the periphery. Palmitate also promotes obesity by acting on the hypothalamus, the central coordinator of energy homeostasis, to dysregulate hypothalamic feeding neuropeptides and induce ER stress and inflammatory signaling. We hypothesized that palmitate would alter hypothalamic miRNAs that control genes involved in energy homeostasis thereby contributing to the obesity‐promoting effects of palmitate. We found that palmitate upregulated 20 miRNAs and downregulated six miRNAs in the orexigenic NPY/AgRP‐expressing mHypoE‐46 cell line. We focused on delineating the roles of miR‐2137 and miR‐503‐5p, as they were strongly up‐ and downregulated by palmitate, respectively. Overexpression of miR‐2137 increased Npy mRNA levels and downregulated Esr1 levels, while increasing C/ebpβ and Atf3 mRNA. Inhibiting miR‐2137 had the opposite effect, except on Npy, which was unchanged. The most downregulated miRNA by palmitate, miR‐503‐5p, negatively regulated Npy mRNA levels. Exposure to the unsaturated fatty acids oleate or docosahexaenoic acid completely or partially blocked the effects of palmitate on miR‐2137 and miR‐503‐5p as well as Npy, Agrp, Esr1, C/ebpβ and Atf3. MicroRNAs may therefore contribute to palmitate actions in dysregulating NPY/AgRP neurons. Effectively combating the deleterious effects of palmitate is crucial to help prevent or reduce the impact of obesity.

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Section: Unsaturated Fatty Acids Oleate and Dha Prevent Palmitate-med...mentioning

confidence: 99%

Palmitate alters miR‐2137 and miR‐503‐5p to induce orexigenic Npy in hypothalamic neuronal cell models: Rescue by oleate and docosahexaenoic acid

McIlwraith

Belsham

2023

J Neuroendocrinology

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“…The authors reported that DHA administration reduced both energy intake and body weight gain. Moreover, it ameliorated the HFD-induced hypothalamic inflammation and improved the central leptin's action in regulating hepatic lipid metabolism (Cheng et al, 2020). Using the same in vivo model, other study observed that fish oil supplementation also protects mice against the anxiogenic and depressive-like effects of HFD (Demers et al, 2020).…”

Section: Hypothalamusmentioning

confidence: 82%

Role of bioactive lipids in obesity

Salsinha¹,

Rodriguez‐Alcalá²,

Pimentel³

et al. 2023

Bioactive Lipids

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“…Furthermore, Oh Da et al (2010) reported that DHA stimulation of GPR120 inhibits both TLR 2/3/4 and the TNF-α proinflammatory cascade. Recently, DHA intracerebroventricular injection in male C57BL/6J mice ameliorated the HFD-induced hypothalamic inflammation (Cheng et al, 2020). Some in vitro studies have also reported relevant results in microglia cell lines: DHA was able to reverse LPS inflammatory effects in N9 microglia cells (Chang et al, 2015;De Smedt-Peyrusse et al, 2008).…”

Section: Obesity and Neuroinflammation: The Dietary Fatty Acids Rolementioning

confidence: 97%

The pro- and antiinflammatory activity of fatty acids

Salsinha

Socodato²,

Relvas³

et al. 2023

Bioactive Lipids

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DHA reduces hypothalamic inflammation and improves central leptin signaling in mice

Cited by 18 publications

References 62 publications

Palmitate alters miR‐2137 and miR‐503‐5p to induce orexigenic Npy in hypothalamic neuronal cell models: Rescue by oleate and docosahexaenoic acid

Palmitate alters miR‐2137 and miR‐503‐5p to induce orexigenic Npy in hypothalamic neuronal cell models: Rescue by oleate and docosahexaenoic acid

Role of bioactive lipids in obesity

The pro- and antiinflammatory activity of fatty acids

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