scholarly journals The Mechanism of Fos and Leptin Receptor in Neural Tube Development of Offspring Under The Regulation of Energy Balance

Author(s):  
Ting Li ◽  
Quan Huo ◽  
Zhi Guo Lu ◽  
Xin Ran Xing ◽  
Lu Ding ◽  
...  

Abstract Background The occurrence of neural tube defects is a complex process in which genes, internal and external environment and other factors jointly influence and occur interactively. In this experiment, animal models of different energy balance states are constructed. To explore the mechanism of fos and leptin-leptin receptor during neural tube development of offspring under different energy states and its effect on neural tube development of offspringMethods Using gene identification technology to obtain Mex3c+/- negative energy balance mice and high-fat diet to obtain positive energy balance mice, and obtain E10.5d, E12.5d, E14.5d embryos. We will verify the expression of fos, leptin, LEPR, nestin, PAX3, and H3K27me3 proteins in the neural tube of the offspring through relevant experimental methods.Results We have successfully constructed animal models, Control group (18.82g±1.54g), Mex3c group (18.84g±1.08g), HFD group (22.61g±1.10g). Neural tube HE staining showen that compared with the Control group, the neuronal maturity of the Mex3c group and the HFD group was reduced. Immunohistochemical staining showed that both fos and leptin were expressed on the nucleus, and LEPR was expressed on the cell membrane. Western blot experiments showed that compared with the Control group, the Mex3c group and the HFD group had low expression of fos protein (P<0.01), the Mex3c group had high expression of LEPR protein (P<0.01) and the HFD group had high expression of LEPR protein (P<0.01). Immunostaining experiments showed that nestin was expressed in nerve fibers, and PAX3 and H3K27me3 were both expressed in the nucleus. Western blooting experiment showed that compared with the Control group, the Mex3c group had high expression of nestin protein (P<0.01), PAX3 protein (P<0.01), H3K27me3 (P<0.01), and the HFD group had high expression of nestin protein (P<0.01). ) And PAX3 protein (P<0.01), H3K27me3 (P<0.01).ConclusionsMex3c regulates leptin and LEPR by enhancing the expression of fos mRNA to participate in the neural tube development process of offspring. The neural tube nestin, PAX3, and H3K27me3 of the offspring of Mex3c+/- mice and high-fat diet mice continue to be highly expressed. Mex3c+/- mice express low leptin, and high-fat diet mice highly express leptin; preliminary reveals the regulation of different energy states Leptin-LEPR is involved in the process of neurodevelopment. Mex3c mutant mice and mice on a high-fat diet lead to decreased neurodevelopmental maturity.

2017 ◽  
Vol 52 (3) ◽  
pp. 174
Author(s):  
Purwo Sri Rejeki ◽  
Harjanto Harjanto ◽  
Raden Argarini ◽  
Imam Subadi

The aim of this study was to determine the comparative effects of EA (EA) on the CV12, ST36 and ST40 to weight gain prevention over the short-term regulation of energy balance. The study was conducted with a completely randomized design. Rats were divided into five groups: negative control group (no treatment, n=5), positive control (sham EA/back, n=5), EA CV 12 (n=6), EA ST 36 (n=6) and EA ST 40 (n=7). Rats were exposed to high-fat diet for two weeks and EA was simultaneously performed once daily, five days a week for two weeks with 2 Hz, for 10 minutes with continuous wave. Body weight, BMI, front limb circumference and rear were measured during study. Levels of blood glucose, cholesterol, triglycerides, LDL and HDL were measured at the end of the study; which reflects the short-term regulation of energy homeostasis. For weight loss, EA CV12, ST36 and ST40 group have lost weight significantly compared to the negative and positive control group. The ST40 group has a significant decrease than ST36 and CV12. The most significant decrease in BMI found in the ST40 group. EA did not affect blood glucose levels, but modulated blood lipid profile. In ST 40 group there was a significant decrease in cholesterol, LDL and triglycerides. EA at point ST 40 is potential in preventing increased body weight and BMI in rats exposed to high-fat diet compared to the CV 12 and ST 36. ST 40 is a point with a potential of lowering LDL and triglycerides serum so that it can play a role in the short term regulation of energy homeostasis but also in the prevention of dyslipidemia.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2501
Author(s):  
Maihemuti Mijiti ◽  
Ryosuke Mori ◽  
Bingyu Huang ◽  
Kenichiro Tsukamoto ◽  
Keisuke Kiriyama ◽  
...  

Dietary protamine can ameliorate hyperlipidemia; however, the protamine-derived active peptide and its hypolipidemic mechanism of action are unclear. Here, we report the discovery of a novel anti-obesity and hypocholesterolemic peptide, RPR (Arg-Pro-Arg), derived from protamine in mice fed a high-fat diet for 50 days. Serum cholesterol levels were significantly lower in the protamine and RPR groups than in the control group. White adipose tissue weight was significantly decreased in the protamine and RPR groups. The fecal excretion of cholesterol and bile acid was significantly higher in the protamine and RPR groups than in the control group. We also observed a significant decrease in the expression of hepatic SCD1, SREBP1, and adipocyte FAS mRNA, and significantly increased expression of hepatic PPARα and adipocyte PPARγ1 mRNA in the protamine group. These findings demonstrate that the anti-obesity effects of protamine are linked to the upregulation of adipocyte PPARγ1 and hepatic PPARα and the downregulation of hepatic SCD1 via SREBP1 and adipocyte FAS. RPR derived from protamine has a crucial role in the anti-obesity action of protamine by evaluating the effective dose of adipose tissue weight loss.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takuya Kawamura ◽  
Hiroaki Tanaka ◽  
Ryota Tachibana ◽  
Kento Yoshikawa ◽  
Shintaro Maki ◽  
...  

AbstractWe aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 302
Author(s):  
Ahtesham Hussain ◽  
Jin Sook Cho ◽  
Jong-Seok Kim ◽  
Young Ik Lee

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.


2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.


2016 ◽  
Vol 48 (7) ◽  
pp. 491-501 ◽  
Author(s):  
Madeliene Stump ◽  
Deng-Fu Guo ◽  
Ko-Ting Lu ◽  
Masashi Mukohda ◽  
Xuebo Liu ◽  
...  

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NESCre/PPARγ-P467L) or selectively in POMC neurons (POMCCre/PPARγ-P467L). Whereas POMCCre/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMCCre/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMCCre/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMCCre/PPARγ-WT, but not POMCCre/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Darren Mehay ◽  
Sarah Bingaman ◽  
Yuval Silberman ◽  
Amy Arnold

Angiotensin (Ang)-(1-7) is a protective hormone of the renin-angiotensin system that improves insulin sensitivity, glucose tolerance, and energy balance in obese rodents. Our recent findings suggest that Ang-(1-7) activates mas receptors (MasR) in the arcuate nucleus of the hypothalamus (ARC), a brain region critical to control of energy balance and glucose homeostasis, to induce these positive metabolic effects. The distribution of MasR in the ARC and their role in metabolic regulation, however, is unknown. We hypothesized: (1) MasR are expressed in the ARC; and (2) deletion of ARC MasR leads to worsened metabolic outcomes following high fat diet (HFD). To test this, male and female C57Bl/6J mice were fed a 60% HFD or matched control diet ad libitum for 12 weeks. RNAscope in situ hybridization was performed on coronal ARC sections in rostral-middle-caudal regions to determine percentage of MasR positive neurons (n=5/group). In a second experiment, we assessed body composition and insulin and glucose tolerance in transgenic mice with deletion of MasR in ARC neurons (MasR-flox with AAV5-hsyn-GFP-Cre). RNAscope revealed a wide distribution on MasR-positive cells throughout the rostral to caudal extent of the ARC. The average percentage of MasR positive neurons was increased in females versus males, with HFD tending to increase MasR expression in both sexes (control diet male: 11±2; control diet female: 17±3; HFD male: 15±5; HFD female: 24±2; p sex : 0.030; p diet : 0.066; p int : 0.615; two-way ANOVA). Deletion of MasR in ARC neurons worsened insulin sensitivity in HFD but not control diet females (area under the curve for change in glucose from baseline: -1989±1359 HFD control virus vs. 2530±1762 HFD Cre virus; p=0.016), while fasting glucose, glucose tolerance, and body composition did not change. There was no effect of ARC MasR deletion on metabolic outcomes in control diet or HFD male mice. These findings suggest females have more MasR positive neurons in the ARC compared to males, which may be a sex-specific protective mechanism for glucose homeostasis. While further studies are needed to explore the role of ARC MasR in metabolic regulation, these findings support targeting Ang-(1-7) as an innovative strategy in obesity.


Author(s):  
Rizka Veni ◽  
Awal Prasetyo ◽  
Muflihatul Muniroh

This study aims to analyze the effect of combination of motor vehicle particular matter exposure and high-fat diet in kidney histopathology, creatinine levels, and MDA levels in Wistar rats. This study used a posttest-only control group design. Eighteen healthy male Wistar rats were divided into three groups. The intervention groups received motor vehicle fume exposure for 100 s with normal diet (X1) or high-fat diet (X2), and the control group received no exposure (C). Data analysis was processed with a SPSS 25.0 computer program by using the one-way ANOVA test followed by post hoc LSD. The degree of kidney histopathological damage showed significant differences between the X1 and X2 groups when compared with the control group (p < 0.05). The results of the creatinine level examination found a significant difference between the X2 and C groups (p < 0.05) and the treatment groups X1 and X2 (p < 0.05). The results of kidney MDA level examination showed a significant difference between the treatment groups (X1 and X2) and the control group (p < 0.05). The combination of particular matter of motor vehicle fumes exposure and high-fat diet could induce kidney damage through histopathological change and increased creatinine levels and kidney MDA levels in Wistar rats.


Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2202
Author(s):  
Micaelle Oliveira de Luna Freire ◽  
Luciana Caroline Paulino do Nascimento ◽  
Kataryne Árabe Rimá de Oliveira ◽  
Alisson Macário de Oliveira ◽  
Thiago Henrique Napoleão ◽  
...  

High-fat diet (HFD) consumption has been linked to dyslipidemia, low-grade inflammation and oxidative stress. This study investigated the effects of a mixed formulation with Limosilactobacillusfermentum 139, L. fermentum 263 and L. fermentum 296 on cardiometabolic parameters, fecal short-chain fatty acid (SCFA) contents and biomarkers of inflammation and oxidative stress in colon and heart tissues of male rats fed an HFD. Male Wistar rats were grouped into control diet (CTL, n = 6), HFD (n = 6) and HFD with L. fermentum formulation (HFD-Lf, n = 6) groups. The L.fermentum formulation (1 × 109 CFU/mL of each strain) was administered twice a day for 4 weeks. After a 4-week follow-up, biochemical parameters, fecal SCFA, cytokines and oxidative stress variables were evaluated. HFD consumption caused hyperlipidemia, hyperglycemia, low-grade inflammation, reduced fecal acetate and propionate contents and increased biomarkers of oxidative stress in colon and heart tissues when compared to the CTL group. Rats receiving the L. fermentum formulation had reduced hyperlipidemia and hyperglycemia, but similar SCFA contents in comparison with the HFD group (p < 0.05). Rats receiving the L. fermentum formulation had increased antioxidant capacity throughout the colon and heart tissues when compared with the control group. Administration of a mixed L. fermentum formulation prevented hyperlipidemia, inflammation and oxidative stress in colon and heart tissues induced by HFD consumption.


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