ArticleHepatology (Baltimore, Md.)2016
Hypothalamic kappa opioid receptor mediates both diet-induced and melanin concentrating hormone-induced liver damage through inflammation and endoplasmic reticulum stress.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Hepatic Olfr734 Deficiency Worsens Hepatic Glucose Metabolism and Induces MASLD in Mice.Nutrients · 2025Article
- The effects of ghrelin and LEAP-2 in energy homeostasis are modulated by thermoneutrality, high-fat diet and aging.Journal of endocrinological investigation · 2024Article
- Activation of the PERK-CHOP signaling pathway during endoplasmic reticulum stress contributes to olanzapine-induced dyslipidemia.Acta pharmacologica Sinica · 2024Article
- Article
- Kappa opioid receptor activation increases thermogenic energy expenditure which drives increased feeding.iScience · 2023Article
- Kappa-Opioid Receptor Blockade Ameliorates Obesity Caused by Estrogen Withdrawal via Promotion of Energy Expenditure through mTOR Pathway.International journal of molecular sciences · 2022Article
- Deletion of RNF186 expression suppresses diet-induced hepatic steatosis by regulating insulin activity.iScience · 2022Article
- Multifaceted actions of melanin-concentrating hormone on mammalian energy homeostasis.Nature reviews. Endocrinology · 2021Review
- Characteristics of opioid prescribing to outpatients with chronic liver diseases: A call for action.PloS one · 2021Article
- MCH Regulates SIRT1/FoxO1 and Reduces POMC Neuronal Activity to Induce Hyperphagia, Adiposity, and Glucose Intolerance.Diabetes · 2019Article
- Hypothalamic dopamine signaling regulates brown fat thermogenesis.Nature metabolism · 2019Article
- Article
- Vagal afferents contribute to sympathoexcitation-driven metabolic dysfunctions.The Journal of endocrinology · 2019Article
- Orexins/Hypocretins: Key Regulators of Energy Homeostasis.Frontiers in endocrinology · 2019Review
- Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress.Cell reports · 2018Article
- Regulation of Chemerin and CMKLR1 Expression by Nutritional Status, Postnatal Development, and Gender.International journal of molecular sciences · 2018Article
- Article
- Pharmacological stimulation of p53 with low-dose doxorubicin ameliorates diet-induced nonalcoholic steatosis and steatohepatitis.Molecular metabolism · 2018Article
- Hypothalamic GRP78, a new target against obesity?Adipocyte · 2018Review
- Hepatic p63 regulates steatosis via IKKβ/ER stress.Nature communications · 2017Article
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Authors and funding
19 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledThe opioid system is widely known to modulate the brain reward system and thus affect the behavior of humans and other animals, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (κOR) and adenoviral vectors overexpressing or silencing κOR were stereotaxically delivered in the lateral hypothalamic area (LHA) of rats. Vagal denervation was performed to assess its effect on liver metabolism. Endoplasmic reticulum (ER) stress was inhibited by pharmacological (tauroursodeoxycholic acid) and genetic (overexpression of the chaperone glucose-regulated protein 78 kDa) approaches. The peripheral effects on lipid metabolism were assessed by histological techniques and western blot. We show that in the LHA κOR directly controls hepatic lipid metabolism through the parasympathetic nervous system, independent of changes in food intake and body weight. κOR colocalizes with melanin concentrating hormone receptor 1 (MCH-R1) in the LHA, and genetic disruption of κOR reduced melanin concentrating hormone-induced liver steatosis. The functional relevance of these findings was given by the fact that silencing of κOR in the LHA attenuated both methionine choline-deficient, diet-induced and choline-deficient, high-fat diet-induced ER stress, inflammation, steatohepatitis, and fibrosis, whereas overexpression of κOR in this area promoted liver steatosis. Overexpression of glucose-regulated protein 78 kDa in the liver abolished hypothalamic κOR-induced steatosis by reducing hepatic ER stress.
conclusionsThis study reveals a novel hypothalamic-parasympathetic circuit modulating hepatic function through inflammation and ER stress independent of changes in food intake or body weight; these findings might have implications for the clinical use of opioid receptor antagonists. (Hepatology 2016;64:1086-1104).
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