ArticleJournal of neurophysiology2015
Brain-mediated antidiabetic, anorexic, and cardiovascular actions of leptin require melanocortin-4 receptor signaling.
Article in Journal of neurophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system.Clinical science (London, England : 1979) · 2026Review
- Is Hypothalamic Dysfunction a Cause of Type II Diabetes Mellitus?Neuroendocrinology · 2026Review
- Reduced contextually induced muscle thermogenesis in rats with calorie restriction and lower aerobic fitness but not monogenic obesity.Temperature (Austin, Tex.) · 2023Article
- Impact of hyperleptinemia during placental ischemia-induced hypertension in pregnant rats.American journal of physiology. Heart and circulatory physiology · 2021Article
- Chronic CNS-mediated cardiometabolic actions of leptin: potential role of sex differences.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism.Endocrine reviews · 2021Review
- Restoration of Cardiac Function After Myocardial Infarction by Long-Term Activation of the CNS Leptin-Melanocortin System.JACC. Basic to translational science · 2021Article
- Administration of recombinant human placental growth factor decreases blood pressure in obese hypertensive pregnant rats.Journal of hypertension · 2020Article
- CNS Regulation of Glucose Homeostasis: Role of the Leptin-Melanocortin System.Current diabetes reports · 2020Review
- Glucose-Lowering by Leptin in the Absence of Insulin Does Not Fully Rely on the Central Melanocortin System in Male Mice.Endocrinology · 2019Article
- Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Control of appetite, blood glucose, and blood pressure during melanocortin-4 receptor activation in normoglycemic and diabetic NPY-deficient mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Sex Differences in Mechanisms of Hypertension Associated With Obesity.Hypertension (Dallas, Tex. : 1979) · 2018Review
- The glucoregulatory actions of leptin.Molecular metabolism · 2017Review
- Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin.American journal of physiology. Endocrinology and metabolism · 2017Article
- Physical Activity, Energy Expenditure, and Defense of Body Weight in Melanocortin 4 Receptor-Deficient Male Rats.Scientific reports · 2016Article
- Nitric oxide synthase-mediated blood pressure regulation in obese melanocortin-4 receptor-deficient pregnant rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
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5 authors at 1 institution in 1 country.
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Abstract
We previously demonstrated that leptin has powerful central nervous system (CNS)-mediated antidiabetic actions. In this study we tested the importance of melanocortin-4 receptors (MC4Rs) for leptin's ability to suppress food intake, increase blood pressure (BP) and heart rate (HR), and normalize glucose levels in insulin-dependent diabetes. MC4R knockout (MC4R-KO) and control wild-type (WT) rats were implanted with intracerebroventricular (ICV) cannula and BP and HR were measured 24 h/day by telemetry. After 5-day control period, an injection of streptozotocin (50 mg/kg, ip) was used to induce diabetes. Eight days after injection, an osmotic pump was implanted subcutaneously and connected to the ICV cannula to deliver leptin (15 μg/day) for 7 days. At baseline, MC4R-KO rats were hyperphagic and 40% heavier than WT rats. Despite obesity, BP was similar (112 ± 2 vs. 111 ± 2 mmHg) and HR was lower in MC4R-KO rats (320 ± 6 vs. 347 ± 5 beats/min). Induction of diabetes increased food intake (30%) and reduced BP (∼17 mmHg) and HR (∼61 beats/min) in WT rats, while food intake, BP, and HR were reduced by ∼10%, 7 mmHg, and 33 beats/min, respectively, in MC4R-KO rats. Leptin treatment normalized blood glucose (437 ± 10 to 136 ± 18 mg/dl), reduced food intake (40%), and increased HR (+60 beats/min) and BP (+9 mmHg) in WT rats. Only modest changes in blood glucose (367 ± 16 to 326 ± 23 mg/dl), food intake (5%), HR (+16 beats/min) and BP (+4 mmHg) were observed in MC4R-KO rats. These results indicate that intact CNS MC4R signaling is necessary for leptin to exert its chronic antidiabetic, anorexic, and cardiovascular actions.
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