Basic Nutritional InvestigationsLeptin effects on feeding-related hypothalamic and peripheral neuronal activities in normal and obese rats
Introduction
In a recent issue of Science1 it was stated that body weight is a lot like the weather: everybody talks about it, but no one seems to be able to do much about it. However, in the past few years researchers have learned a great deal about the physiologic mechanisms that help people keep their energy intake and expenditure in balance. Our knowledge of the part played by the cloned ob-protein (leptin)2 in the regulation of body weight is largely derived from studies performed in rodents and humans.3, 4 Leptin, expressed by the ob gene on white adipocytes, actually plays an important role in the neural (central/peripheral) controls of feeding suppression.5, 6, 7 Leptin receptors are known to be localized in the hypothalamus,8 but its effects on neuronal activity within the feeding-related central (hypothalamic) and/or peripheral nervous systems have not been demonstrated. The purpose of the present study, using normal Wistar and Zucker obese (fa/fa) rats, was to clarify the effects of leptin 1) on neuronal activity in the feeding-related region of the hypothalamus, 2) on vagal hepatic afferents, and 3) on sympathetic efferents to brown and white adipose tissue (BAT/WAT). For this we used anesthetized, brain-slice, and perforate patch-clamp preparations. Some preliminary results have been reported elsewhere.9, 10
Section snippets
Recording of hepatic vagal afferents and BAT/WAT sympathetic efferents
Wistar rats, weighing about 300 g, were used. They were kept in a room at 24°C with illumination for 12 h a day (0700–1900 h). Food, but not water, was removed 12 h before the experiment. Animals were anesthetized by intraperitoneal injection of 1 g/kg urethane, and warmed by a heating pad to maintain the body temperature at about 37°C. After a laparotomy, a catheter was inserted into the portal vein for the administration of this recombinant leptin (PeproTech EC, London, UK, and also donated
Effects of leptin on vagal hepatic afferent neural discharge
It is well known that vagal hepatic afferents perform very important functions in the sending of information from peripheral chemosensors responding to, from metabolic substrate, such as glucose, protein, peptides, and fat, to the feeding-related brain, at least, the hypothalamus. Most of these substances, because of their large molecular weight, have difficulty penetrating the blood-brain barrier and thus do not affect the brain directly. The OB-R (OB receptor), however, the receptor for
Summary
We have revealed the target sites for leptin (as a feedback hormone) using the following evidence:
- 1.
Leptin inhibited (low dose)/augmented (high dose) hepatic vagal afferent activity.
- 2.
Leptin enhanced sympathetic efferent neural activity to both WAT and BAT.
- 3.
Leptin inhibited GSNs in the ACN.
- 4.
Leptin excited GRNs in the VMH (satiety center).
- 5.
Leptin inhibited GSNs in the LHA (feeding center).
- 6.
GSNs in the parvocellular division of the PVN were excited by leptin.
- 7.
Leptin had little or no effect on the
Conclusion
Our results suggest that the feeding-suppression effects of leptin are mediated by its effects on signal transduction through both the central and peripheral nervous systems.
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Cited by (67)
Obese female Zucker rats (fa/fa) exhibit dendritic retraction in neurons in the ventromedial hypothalamic nucleus
2021, Journal of Chemical NeuroanatomyCitation Excerpt :In the present study, we observed that VMH neurons of female OZ rats express dendritic retraction compared to VMH neurons of LE and LZ rats. This phenomenon could be due to the absence of leptin receptor activity because leptin stimulates the activity of different types of neurons in the hypothalamus, including glucose-sensitive parvocellular neurons of the paraventricular nucleus and glucoreceptor neurons of the VMH (Shiraishi et al., 1999). Recent studies indicate that leptin promotes neuronal plasticity in the hippocampus, including events at the synaptic level, neuronal morphological level, glutamate receptor trafficking level, and neuroprotector level, to avoid cellular apoptosis and promote cellular survival (Doherty et al., 2013).
Age-related changes in acute central leptin effects on energy balance are promoted by obesity
2016, Experimental GerontologyCitation Excerpt :On the other hand, the activation of the anabolic neuropeptide Y (NPY) and that of the endogenous melanocortin antagonist agouti-related peptide (AgRP) are suppressed (Baskin et al., 1999; Berglund et al., 2012). In the periphery, leptin also acts on different sites of the afferent vagus (Wang et al., 1997; Gaigé et al., 2002; Shiraishi et al., 1999; Buyse et al., 2001), transmitting information to the brainstem and to the nucleus of the solitary tract (NTS) (Buyse et al., 2001; Grill et al., 2002; Székely and Szelényi, 2005). The responsiveness to leptin has been shown to decline (with consequent hyperleptinemia) during the course of age-related weight gain (Scarpace et al., 2000a) and in obesity of other etiologies at any age (Lin et al., 2000; Myers et al., 2012).
Central leptin and tumor necrosis factor-α (TNFα) in diurnal control of blood pressure and hypertension
2016, Journal of Biological ChemistryCitation Excerpt :As known, leptin-induced STAT3 activation during the initial phase is mediate through leptin receptor activation-induced JAK2-STAT3 cascade (30). This initial phase of leptin signaling is fast and excites neurons to rapidly induce biological actions (46), some of which might be independent of STAT3 transcriptional program (47–49). In contrast to the short time window of initial leptin signaling, the second phase of leptin-activated STAT3 is moderate but tonic, presumably being involved in certain chronic functions of leptin, such as immune regulation.
The neuroanatomical function of leptin in the hypothalamus
2014, Journal of Chemical NeuroanatomyLeptin and aging: Review and questions with particular emphasis on its role in the central regulation of energy balance
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2010, Molecular and Cellular Endocrinology