Hypothalamic γ-melanocyte stimulating hormone gene delivery reduces fat mass in male mice

Eerola, Kim; Virtanen, S; Vähätalo, Laura H.; Ailanen, Liisa; Cai, Minying; Hruby, Victor J.; Savontaus, Mikko; Savontaus, Eriika

doi:10.1530/joe-18-0009

Cited by 5 publications

(5 citation statements)

References 52 publications

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“…It is known that unpredictable mild stress decreases the neural activity of hippocampal cells and the proliferation of hippocampal progenitor cells, and that these activities can be increased by the administration of antidepressants 10-12 . We then examined the hippocampal c-Fos protein-positive cells, known as a general neural activity marker [13][14][15] , and the effects of the proliferation of progenitor cells in vivo and in vitro. Brain-derived neurotrophic factor (BDNF) is known to induce the proliferation of hippocampal progenitor cells and has an antidepressant-like effect [16][17][18] .…”

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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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confidence: 99%

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Maekawa

Uchida

Ohinata

2020

Sci Rep

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“…The cDNA was the template for the amplification reaction of expression detection by qRT-PCR (Roche, Mannheim, Germany) using gene-specific primers. The primer sequences were (5′→3′) COL1A1 F-AGCCTCTCCATCTTTGCCAGCA and R-GATTCCCTGGACCTAAAGGTGC [ 22 ], COL1A2 F-CCTGGTGCTAAAGGAGAAAGAGG and R-ATCACCACGACTTCCAGCAGGA [ 22 ], COL3A1 F-TGGTCTGGAAGGAATGCCTGGA and R-TCTTCCCTGGGACACCATCAG [ 22 ], FGF1 F-ATGGCACAGGTGGATGGGACAAG and R-TAAAAGCCCGTCGGTGTCCATG [ 22 ], FGF7 F-CTGTCGAACACAGTGGTACCTG and R-CCAACTGCCACTGTCCTGATTTC [ 22 ], GAPDH F-GTCTCCTCTGACTTCAACAGCG and R-ACCACCCTGTTGTGTAGCCAA [ 22 ], TYR F-CCATGACAAATCCAGAACCC and R-GGACTAGCAAATCCTTCCAG [ 23 ], α-MSH F-GTCCTCAGAAAGCTTCCTTTCCGC and R-CGTTGCCTGGAAACCGCGGCGTCTC [ 24 ], NRF2 F-TTCTGTTGCTCAGGTAGCCCC and R-TCAGTTTGGCTTCTGGACTTGG [ 25 ], HLE F-GCTGGAGCCCTCAGTTGTGGG and R-TGTTGGGTAGAATGGTGCCGG [ 26 ]. The 20 µL mixture reaction contained 5 µL 4× CAPITAL qPCR green mix LRox (Biotech rabbit, Berlin, Germany), 0.5 µL forward primer and 0.5 µL reverse primer (10 µM), 12 µL PCR grade water and 2 µL cDNA.…”

Section: Methodsmentioning

confidence: 99%

Investigation of Morinda citrifolia Activities through Pinoresinol and α-EG Related Gene Expression

Sudmoon

Kaewdaungdee

Ameamsri

et al. 2022

Plants

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α-EG is a unique substance that was first found in the leaves and fruits of Morinda citrifolia (Mc) growing in Thailand using GC-MS at 52.33% and 54.12%. It was then concentrated and its abundance quantified, along with that of pinoresinol, via GC, compared to the standards in leaves, ufp, rfp, rawfs, and seeds. α-EG and pinoresinol, which have collagen stimulating, skin whitening, and an inhibitory effect on wrinkle formation, were found in different concentrations and amounts. Three different concentrations of the five Mc part extracts were tested on NHDF for gene expression related to the aforementioned activities, COL1A1, COL1A2, and COL3A1, FGF1 and FGF7 by qRT-PCR. The results showed various expression levels, both stimulatory and inhibitory, with different concentrations of plant parts and genes. Similar results were revealed when the experiments were performed with Morus alba (Ma), which was found to contain 20.48 g protein p/100 g leaves at concentrations of 3.11 mg/mL. The studied Mc parts seem to have advantages based on the stated objectives, gene type and level of activity of each plant part. Rawfs and leaves supplemented with Ma samples were selected for toxicity tests with PBMCs. The lack of both cell and DNA toxicity from the rawfs indicated that they can be used safely.

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“…Each segment produces one form of MSH. Mutations in POMC have been shown to cause severe, earlyonset obesity, and all of the major melanocortins (ACTH, α-MSH, β-MSH and γ-MSH) have been shown to ameliorate obesity in animal models [6][7][8][9][10][11][12][13][14]. Melanocortins activate a group of five G-coupled protein receptors (termed melanocortin receptors, MCR) on the cell surface leading to a signal transduction cascade in the cell.…”

Section: Melanocortins and The Pomc Systemmentioning

confidence: 99%

“…A level of extended satiety can thus be reached, allowing for an amelioration of obesity and its consequent conditions, such as type II diabetes and its associated insulin resistance. The administration of various synthetic melanocortin peptides has been successfully used in this manner in multiple animal and human studies [6][7][8][9]11,12,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41].…”

Section: Melanocortins and Leptin: A Potential Downstream Advantagementioning

confidence: 99%

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Melanocortins and Their Potential for the Treatment, Prevention and Amelioration of Complications of Diabetes

Robinson,

Pickering

2024

Diabetology

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Diabetes mellitus (type I and II) is an advancing global health problem, concerningly increasing in prevalence in most of the developed and developing world. Current therapies, such as the subcutaneous injection of insulin, are invasive and require a close monitoring of blood glucose levels to prevent hypo- or hyperglycaemia from occurring. Despite an inexorable search for a cure since Banting and Best discovered and purified insulin in 1921, insulin remains a solitary insula, still the gold standard for treatment of type I and late-stage type II diabetes mellitus. Apropos of complications, diabetes causes a myriad of secondary maladies, ranging from diabetic kidney disease, diabetic retinopathy and diabetic neuropathy to erectile dysfunction and peripheral vascular disease. While scientists continue to interminably tinker with perfecting mechanical insulin pumps or dampening the immune response to pancreatic beta cells, an important aspect of the aetiology of diabetes should not be neglected, that of the metabolism. At its heart, diabetes can arguably be considered a metabolic disease, and this review suggests a return to focusing on preventing and treating diabetes by focussing on its metabolic causes. This narrative review summarises the potential of a recent class of synthetic peptides, the melanocortins, to help prevent and treat the complications of diabetes mellitus. The review summarises recent work showing the potential benefits of the melanocortins in treating diabetic complications through various pathways.

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Hypothalamic γ-melanocyte stimulating hormone gene delivery reduces fat mass in male mice

Cited by 5 publications

References 52 publications

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Investigation of Morinda citrifolia Activities through Pinoresinol and α-EG Related Gene Expression

Melanocortins and Their Potential for the Treatment, Prevention and Amelioration of Complications of Diabetes

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