Hypothalamic NPFFR2 attenuates central insulin signaling and its knockout diminishes metabolic dysfunction in mouse models of diabetes mellitus

Lin, Ya-Tin; Wu, Kuan-Hsuan; Jhang, Jie-Jhu; Jhang, Jie-Lan; Yu, Zachary; Tsai, Sze-Chi; Chen, Jin-Chung; Hsu, Po-Hung; Li, Hui-Yun

doi:10.1016/j.clnu.2024.01.013

Cited by 2 publications

(1 citation statement)

References 36 publications

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“…Data are controversial regarding mice lacking NPFFR2. Npffr2 null mice maintained on a high-fat diet were reportedly obese [279], but these animals showed improved metabolic symptoms in mouse models of diabetes mellitus [280]. In harmony with the findings detected in ligand-deficient animals, NPFFR2-deficient animals were more resistant to stress-induced anxiety-like behavior than wild-type animals [281].…”

Section: Functional Role Of Rfamide Peptides Based Upon Knockout (Ko)...mentioning

confidence: 54%

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Kovács,

Szabó,

László

et al. 2024

Cells

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The RFamide peptide family is a group of proteins that share a common C-terminal arginine–phenylalanine–amide motif. To date, the family comprises five groups in mammals: neuropeptide FF, LPXRFamides/RFamide-related peptides, prolactin releasing peptide, QRFP, and kisspeptins. Different RFamide peptides have their own cognate receptors and are produced by different cell populations, although they all can also bind to neuropeptide FF receptors with different affinities. RFamide peptides function in the brain as neuropeptides regulating key aspects of homeostasis such as energy balance, reproduction, and cardiovascular function. Furthermore, they are involved in the organization of the stress response including modulation of pain. Considering the interaction between stress and various parameters of homeostasis, the role of RFamide peptides may be critical in the development of stress-related neuropathologies. This review will therefore focus on the role of RFamide peptides as possible key hubs in stress and stress-related psychopathologies. The neurotransmitter coexpression profile of RFamide-producing cells is also discussed, highlighting its potential functional significance. The development of novel pharmaceutical agents for the treatment of stress-related disorders is an ongoing need. Thus, the importance of RFamide research is underlined by the emergence of peptidergic and G-protein coupled receptor-based therapeutic targets in the pharmaceutical industry.

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Section: Functional Role Of Rfamide Peptides Based Upon Knockout (Ko)...mentioning

confidence: 54%

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Kovács,

Szabó,

László

et al. 2024

Cells

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Protective Effects of Exogenous Melatonin Administration on White Fat Metabolism Disruption Induced by Aging and a High-Fat Diet in Mice

Lv,

Ren,

Chen

et al. 2024

Antioxidants

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Obesity has emerged as a major risk factor for human health, exacerbated by aging and changes in dietary habits. It represents a significant health challenge, particularly for older people. While numerous studies have examined the effects of obesity and aging on fat metabolism independently, research on their combined effects is limited. In the present study, the protective action against white fat accumulation after a high-fat diet (HFD) exerted by exogenous melatonin, a circadian hormone endowed with antioxidant properties also involved in fat metabolism, was investigated in a mouse model. For this purpose, a battery of tests was applied before and after the dietary and melatonin treatments of the animals, including epididymal white adipose tissue (eWAT) histological evaluations, transcriptomic and lipidomic analyses, real-time PCR tests, immunofluorescence staining, Western blot, the appraisal of serum melatonin levels, and transmission electron microscopy. This study found that aged mice on a high-fat diet (HFD) showed increased lipid deposition, inflammation, and reduced antioxidant glutathione (GSH) levels compared to younger mice. Lipidomic and transcriptomic analyses revealed elevated triglycerides, diglycerides, ceramides, and cholesterol, along with decreased sphingomyelin and fatty acids in eWAT. The genes linked to inflammation, NF-κB signaling, autophagy, and lipid metabolism, particularly the melatonin and glutathione pathways, were significantly altered. The aged HFD mice also exhibited reduced melatonin levels in serum and eWAT. Melatonin supplementation reduced lipid deposition, increased melatonin and GSH levels, and upregulated AANAT and MTNR1A expression in eWAT, suggesting that melatonin alleviates eWAT damage via the MTNR1A pathway. It also suppressed inflammatory markers (e.g., TNF-α, NLRP3, NF-κB, IL-1β, and CEBPB) and preserved mitochondrial function through enhanced mitophagy. This study highlights how aging and HFD affect lipid metabolism and gene expression, offering potential intervention strategies. These findings provide important insights into the mechanisms of fat deposition associated with aging and a high-fat diet, suggesting potential intervention strategies.

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Hypothalamic NPFFR2 attenuates central insulin signaling and its knockout diminishes metabolic dysfunction in mouse models of diabetes mellitus

Cited by 2 publications

References 36 publications

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Protective Effects of Exogenous Melatonin Administration on White Fat Metabolism Disruption Induced by Aging and a High-Fat Diet in Mice

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