Spexin Regulates Hypothalamic Leptin Action on Feeding Behavior

Jeong, Bora; Kim, Kwang Kon; Lee, Tae Hwan; Kim, Han Rae; Park, Byong Seo; Park, Jeong Woo; Jeong, Jin Kwon; Seong, Jae Young; Lee, Byung Ju

doi:10.3390/biom12020236

Cited by 18 publications

(10 citation statements)

References 62 publications

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“…Similarly, as shown in Figure 4D, LE supplementation stimulated mRNA expression of spexin which is recently identified neuropeptide involving in energy homeostasis and POMC gene expression (46). Previous research reported that spexin regulated hypothalamic leptin action on POMC gene expression and consequently modulated feeding behavior (46). Thus, our data suggest that LE supplementation can promote anorexigenic signal through POMC neuronal activity in hypothalamus.…”

Section: Discussionsupporting

confidence: 78%

Longan extract suppresses food intake through regulation of POMC/AgRP neuronal activities and endoplasmic reticulum stress in hypothalamus of db/db mice

Kim

et al. 2023

Front. Nutr.

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Type 2 diabetes mellitus (T2DM) is one of the biggest public health issues worldwide and closely related to development of other chronic diseases such as cardiovascular diseases, cancer and neurodegenerative diseases. Considerable percentage of T2DM patients undergo have suffered from binge eating disorder which exacerbates insulin resistance and metabolic challenges. Longan (Dimocarpus longan L.) and its constituents are reported for their various health benefits. However, it is still unknown whether longan fruit supplementation can ameliorate glucose homeostasis and binge eating disorder found in T2DM. The current study aimed to investigate whether longan fruit extract (LE) supplementation can improve diabetic hyperglycemia through modulation of feeding center located in hypothalamus of db/db T2DM mice. As a result, LE supplementation ameliorated fasting blood glucose levels and reduced excessive epididymal fat accumulation. In addition, LE administration improved glucose tolerance and insulin sensitivity in db/db mice. Especially, LE supplemented mice showed less food consumption which was in line with increase of pro-opiomelanocortin (POMC) neuronal activities and decrease of agouti-related peptide (AgRP) neuronal activities. Furthermore, LE supplementation reduced hypothalamic endoplasmic reticulum (ER) stress which was stimulated in db/db mice. As ER stress is a crucial factor involving in appetite control and glucose homeostasis, the effect of LE supplementation on circulating glucose levels and feeding behavior might be mediated by suppression of hypothalamic ER stress. Collectively, these findings suggest that LE could be a potential nutraceutical for improvement of T2DM as well as patients with satiety issues.

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Section: Discussionsupporting

confidence: 78%

Longan extract suppresses food intake through regulation of POMC/AgRP neuronal activities and endoplasmic reticulum stress in hypothalamus of db/db mice

Kim

et al. 2023

Front. Nutr.

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“…We found that the body weights of the control mice injected with vehicle were lower compared to the control mice before injection, which may be resulted from short-term stresses of the animals induced by vehicle injection. This opinion is evidenced by a previous report that the body weights of the mice decreased upon saline injection [63]. It is known that STAT3 in the hypothalamic POMC neuron is a key element of leptin’s action to control appetite and energy homeostasis [28, 30, 53], and phosphorylation at Y705 for activation of hypothalamic STAT3 has been documented to contribute to leptin signaling pathway [30, 44, 64, 65].…”

Section: Discussionmentioning

confidence: 80%

Inhibition of Hypothalamic FTO Activates STAT3 Signal through ERK1/2 Associated with Reductions in Food Intake and Body Weight

Hu¹,

Yan²,

Gao³

et al. 2022

Neuroendocrinology

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Introduction: Fat mass and obesity associated (FTO) gene is strongly associated with obesity which brings to a major health threat. Altered expression of its encoded protein FTO in the hypothalamus has been identified to contribute to central control of appetite and body weight. However, its molecular mechanisms remain elusive. Methods: Mouse hypothalamic POMC cell line N43/5 was treated with FTO inhibitor rhein, FTO shRNA or extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 to inhibit FTO or ERK1/2. Rhein and U0126 were injected into lateral ventricle of the mice by intracerebroventricular cannulation. Western blotting and immunofluorescent assays were performed to monitor protein level. Results: This study identified that inhibition of FTO in N43/5 cells led to phosphorylation of signal transducer and activator of transcription 3 (STAT3) at S727 site and induced p-STAT3-S727 nuclear translocation. We further showed that FTO inhibition promoted phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2); and specific inhibition of ERK1/2 signaling by U0126 could abolish the effect of FTO inhibition on STAT3-S727 phosphorylation and nuclear translocation. Furthermore, we found that inhibition of hypothalamic FTO promoted STAT3-S727 phosphorylation in the hypothalamic arcuate nucleus, and the mice showed reductions in food intake and body weight. In addition, inhibition of hypothalamic ERK1/2 could abolish the effects of FTO inhibition on STAT3-S727 phosphorylation, reductions of food intake and body weight. Conclusion: our in-vitro and in-vivo data suggest that the inhibition of hypothalamic FTO could activate STAT3 through ERK1/2, which is potentially associated with reductions in food intake and body weight.

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“…The novel neuropeptide SPX acts as an important factor in regulating feeding behavior [ 25 , 26 ], long-chain fatty acid uptake [ 27 ], energy utilization [ 27 , 28 ], and body weight regulation [ 29 , 30 ]. Bile acids also show a mediatory role in lipid metabolism and energy balance [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression

Lai

Bai

et al. 2022

Cells

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Spexin (SPX) is a novel peptide involved in glucose and lipid metabolism and suppresses hepatic total bile acid levels by inhibiting hepatic cholesterol 7α-hydroxylase 1 expression. As important mediators for glycolysis/gluconeogenesis and lipid metabolism, the effects of bile acids on SPX expression is yet to be understood. By using SMMC7721 and BEL-7402 cell lines, we screened the effects of bile acids and found that chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) can stimulate SPX gene transcription. Both CDCA and DCA were able to stimulate SPX mRNA expression in the liver but not colon and ileum in mice. In SMMC7721 and BEL-7402 cells, CDCA- and DCA-induced SPX promoter activity was mimicked by bile acid receptor FXR and TGR5 activation and suppressed by FXR and TGR5 silencing. Adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP) activators significantly increased SPX promoter activity whereas the inhibitors for AC/CAMP/protein kinase A (PKA) and mitogen-activated protein kinases (MAPK) pathway attenuated CDCA- and DCA-induced SPX transcription. Thus, CDCA and DCA stimulate SPX expression at the hepatic level through FXR and TGR5 mediated AC/cAMP/PKA and MAPK cascades.

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Spexin Regulates Hypothalamic Leptin Action on Feeding Behavior

Cited by 18 publications

References 62 publications

Longan extract suppresses food intake through regulation of POMC/AgRP neuronal activities and endoplasmic reticulum stress in hypothalamus of db/db mice

Longan extract suppresses food intake through regulation of POMC/AgRP neuronal activities and endoplasmic reticulum stress in hypothalamus of db/db mice

Inhibition of Hypothalamic FTO Activates STAT3 Signal through ERK1/2 Associated with Reductions in Food Intake and Body Weight

Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression

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