Blood-to-brain communication in the hypothalamus for energy intake regulation

Morita-Takemura, Shoko; Wanaka, Akio

doi:10.1016/j.neuint.2019.04.007

Cited by 29 publications

(20 citation statements)

References 120 publications

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“…In addition, centrally administered YL exhibited an antidepressant-like effect. Although endogenous peptide hormones, such as leptin, ghrelin, insulin, and peptide YY, cross the blood-brain barrier (BBB) 23 , it is not clear whether YL crosses the BBB; however, brain-transportable dipeptides have recently been reported 24 . Thus, it cannot be ruled out that YL reaches the brain in dipeptide-form and act on the central nervous system (CNS).…”

Section: Discussionmentioning

confidence: 99%

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Maekawa

Uchida

Ohinata

2020

Sci Rep

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Depression is a worldwide health problem. In the present study, we found that a dipeptide, tyrosyl leucine (Tyr-Leu, YL), administered orally, intracerebroventricularly, or intraperitoneally exhibited a potent antidepressant-like activity in the forced swim and tail suspension tests in naïve mice. YL increased the amount of cells expressing c-Fos, a marker for neuronal activity, in the dentate gyrus of the hippocampus. YL increased bromo-2′-deoxyuridine-positive cells and doublecortin expression in the dentate gyrus of the hippocampus, suggesting that YL enhanced the proliferation of hippocampal progenitor cells in vivo and in vitro. YL did not affect hippocampal mRNA and protein expression of BDNF, which is a regulatory factor of both neurogenesis and depression-like behavior. Intriguingly, YL suppressed activation of the hypothalamo-pituitary-adrenal axis by forced swim stress. Moreover, other aromatic amino acid-leucines, Phe-Leu and Trp-Leu, also exhibited antidepressant-like activities, suggesting that the structure of aromatic amino acid-leucine may be important for antidepressant activity. In addition, bovine milk casein-derived peptide, Tyr-Leu-Gly (YLG), an anxiolytic peptide, exhibited an antidepressant-like activity. Our findings demonstrate that YL exhibits an antidepressantlike effect, moderates the stress response, and induces hippocampal neuronal proliferation through a signal pathway independent of BDnf.A number of bioactive peptides have been found in enzymatic digests of various food proteins, and some of these peptides are known to act on the nervous system. We also reported that bioactive peptides derived from food proteins exhibit anxiolytic-like effects 1-7 , suggesting interactions between food components and the nervous system. Clarification of these interactions is challenging, since the food components, including food protein digests, consist of numerous molecular species. On the other hand, we have found novel bioactive peptides based on the structure-activity relationships of dipeptides. Thus, the discovery of dipeptides with potent activities and the their structure-activity relationships are very important and powerful clues to find novel peptides. Indeed, we initially found that a dipeptide, tyrosyl leucine (Tyr-Leu, YL), had a potent anxiolytic-like effect, comparable to that of diazepam, one of the general anxiolytics, in mice 1 . Thereafter, based on the structure rule required for the anxiolytic activity of YL, novel food-derived peptides have been rapidly been identified. Thus, we focused on dipeptides.Major depressive disorder, one of the most common psychiatric diseases, is characterized by dysregulation of emotion and mood as well as abnormalities of cognitive function, sleep, appetite, and metabolism. It is known to be a leading cause of disability worldwide 8,9 . Anxiolytic molecules often exhibit antidepressant-like effects. Thus, in the current study, we investigated whether YL exhibits antidepressant-like activities using two behavioral tests commonly used to screen ant...

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Section: Discussionmentioning

confidence: 99%

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Maekawa

Uchida

Ohinata

2020

Sci Rep

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“…Morphological analysis revealed that NPGL neurons were localized in the lateroposterior part of the arcuate nucleus (Arc), and their fibers projected to the rostral region of the Arc [18]. The Arc is located close to the median eminence (ME), which is deficient in the blood-brain barrier (BBB) [25]. Indeed, it is well known that some peripheral hormones act on the neurons in the Arc [26–28].…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous infusion of neurosecretory protein GL promotes fat accumulation in mice

Narimatsu

Fukumura

Ukena

et al. 2021

Preprint

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We recently identified a novel small secretory protein, neurosecretory protein GL (NPGL), in the vertebrate hypothalamus. We revealed that NPGL is involved in energy homeostasis using intracerebroventricular infusion in rodents. However, the effect of NPGL through peripheral administration remains to be elucidated and may be important for therapeutic use. In this study, we performed subcutaneous infusion of NPGL in mice for 12 days and found that it accelerated fat accumulation in white adipose tissue (WAT) without increasing in body mass gain and food intake. The mass of the testis, liver, kidney, heart, and gastrocnemius muscle remained unchanged. Analysis of mRNA expression by quantitative reverse transcription-polymerase chain reaction showed that proopiomelanocortin was suppressed in the hypothalamus by the infusion of NPGL. We observed a decreasing tendency in serum triglyceride levels due to NPGL, while serum glucose, insulin, leptin, and free fatty acids levels were unchanged. These results suggest that the peripheral administration of NPGL induces fat accumulation in WAT via the hypothalamus.

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“…They have long processes that project into hypothalamic nuclei and the ME, where they end in close contact to blood vessels and neuronal terminals [13]. In the classical view, tanycytes are grouped according to their localization in the ventricular wall as α1, α2, β1, and β2 tanycytes [14]: α1-tanycytes line the ventricular wall along the ventromedial and dorsomedial nuclei; α2-tanycytes along the arcuate nucleus (AN); β1-tanycytes along the infundibular recess, with their basal projections reaching the lateral regions of the ME and the AN; and β2-tanycytes along the floor of the 3 rd ventricle, with their projections extending inside the ME and contacting fenestrated capillaries [15]. β2-Tanycytes are also connected to each other through tight junctions, forming a physical barrier and preventing uncontrolled diffusion of extracellular compounds from the ME into the cerebrospinal fluid (CSF) [16].…”

Section: Tanycytes In Regulation Of the Hpt Axismentioning

confidence: 99%

“…Although knowledge of the physiological importance of tanycytes has increased in recent years, many questions remain to be answered. The further investigation of how tanycytes influence metabolism [44,64,78], of the transport of substances into [15] and out of the CNS [26,62], and of the sensory function of tanycytes [26,69,75,78] requires that tanycytic subpopulations be investigated. In particular, subtype-specific viral vectors can play a decisive role.…”

Section: Conclusion and Open Questionsmentioning

confidence: 99%

The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

Müller-Fielitz

Schwaninger

2019

Exp Clin Endocrinol Diabetes

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Thyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.

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Blood-to-brain communication in the hypothalamus for energy intake regulation

Cited by 29 publications

References 120 publications

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Subcutaneous infusion of neurosecretory protein GL promotes fat accumulation in mice

The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

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