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Differential role of leptin receptors at the hypothalamic paraventricular nucleus in tonic regulation of food intake and cardiovascular functions

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Journal of Biomedical Science

Abstract

Leptin plays an important role in the central regulation of body weight and arterial pressure via activation of leptin receptors (Ob-Rs) in the hypothalamic area, including the hypothalamic paraventricular nucleus (PVN). The present study was undertaken to investigate whether endogenous leptin in the PVN plays a dual role in the tonic regulation of body weight and arterial pressure. Adult, male normal-weight Sprague-Dawley rats, which were anesthetized and maintained with propofol, were used. A direct bilateral microinjection into the PVN of an antisense oligonucleotide against Ob-R mRNA (ASON1, 50 pmol) significantly increased the daily food intake and body weight gain, effects which lasted for at least 14 days. The same treatment, on the other hand, had no appreciable effect on the basal mean systemic arterial pressure (SAP), heart rate (HR), or power density of the vasomotor components of SAP signals, the experimental index of neurogenic sympathetic vasomotor tone. ASON1 treatment also exerted an insignificant effect on the baroreceptor reflex control of HR. Western blot analysis revealed that a bilateral microinjection into the PVN of ASON1 (50 pmol) significantly decreased the expression of the Ob-R protein in the hypothalamus. The same treatment also attenuated hypertension, tachycardia, and the increase in the power density of the vasomotor components of the SAP signals induced by exogenous bilateral application of leptin (5 or 50 ng) into the PVN. Control application of sense (SON, 50 pmol) or a scrambled antisense Ob-R oligonucleotide (ASON2, 50 pmol) into the bilateral PVN promoted no discernible effect on Ob-R protein expression in the hypothalamus, on daily food intake, or on cardiovascular performance. Our results indicate that whereas the Ob-Rs in the PVN are involved in the tonic regulation of food intake, they might not be actively involved in the tonic regulation of cardiovascular functions.

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Authors and Affiliations

  1. Department of Pharmacy, Tajen Institute of Technology, Pintung

    Cheng-Dean Shih

  2. Department of Medical Education and Research, Taipei Veterans General Hospital, Taipei

    Lo-Chun Au

  3. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC

    Julie Y. H. Chen PhD

  4. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 813, Kaohsiung, Taiwan (ROC)

    Julie Y. H. Chen PhD

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  1. Cheng-Dean Shih
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Shih, CD., Au, LC. & Chen, J.Y.H. Differential role of leptin receptors at the hypothalamic paraventricular nucleus in tonic regulation of food intake and cardiovascular functions. J Biomed Sci 10, 367–378 (2003). https://doi.org/10.1007/BF02256428

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