scholarly journals Synergistic effect of leptin and lipidized PrRP on metabolic pathways in ob/ob mice

2020 ◽  
Vol 64 (2) ◽  
pp. 77-90 ◽  
Author(s):  
Lucia Kořínková ◽  
Martina Holubová ◽  
Barbora Neprašová ◽  
Lucie Hrubá ◽  
Veronika Pražienková ◽  
...  

Lack of leptin production in ob/ob mice results in obesity and prediabetes that could be partly reversed by leptin supplementation. In the hypothalamus, leptin supports the production of prolactin-releasing peptide (PrRP), an anorexigenic neuropeptide synthesized and active in the brain. In our recent studies, the palmitoylated PrRP analog palm11-PrRP31 showed a central anorexigenic effect after peripheral administration. This study investigates whether PrRP could compensate for the deficient leptin in ob/ob mice. In two separate experiments, palm11-PrRP31 (5 mg/kg) and leptin (5 or 10 μg/kg) were administered subcutaneously twice daily for 2 or 8 weeks to 8- (younger) or 16-(older) week-old ob/ob mice, respectively, either separately or in combination. The body weight decreasing effect of palm11-PrRP31 in both younger and older ob/ob mice was significantly powered by a subthreshold leptin dose, the combined effect could be then considered synergistic. Leptin and palm11-PrRP31 also synergistically lowered liver weight and blood glucose in younger ob/ob mice. Reduced liver weight was linked to decreased mRNA expression of lipogenic enzymes. In the hypothalamus of older ob/ob mice, two main leptin anorexigenic signaling pathways, namely, Janus kinase, signal transducer and activator of transcription-3 activation and AMP-activated protein kinase de-activation, were induced by leptin, palm11-PrRP31, and their combination. Thus, palm11-PrRP31 could partially compensate for leptin deficiency in ob/ob mice. In conclusion, the results demonstrate a synergistic effect of leptin and our lipidized palm11-PrRP31 analog.

2020 ◽  
Vol 11 ◽  
Author(s):  
Yujie Gong ◽  
Wentao Lyu ◽  
Xingfen Shi ◽  
Xiaoting Zou ◽  
Lizhi Lu ◽  
...  

During the process of fatty liver production by overfeeding, the levels of endogenous metabolites in the serum of geese would change dramatically. This study investigated the effects of overfeeding on serum metabolism of Landes geese and the underlying mechanisms using a metabolomics approach. Sixty Landes geese of the same age were randomly divided into the following three groups with 20 replicates in each group: D0 group (free from gavage); D7 group (overfeeding for 7 days); D25 group (overfeeding for 25 days). At the end of the experiment, 10 geese of similar weight from each group were selected for slaughter and sampling. The results showed that overfeeding significantly increased the body weight and the liver weight of geese. Serum enzymatic activities and serum lipid levels were significantly enhanced following overfeeding. Gas chromatography time-of-flight/mass spectrometry (GC-TOF/MS) was employed to explore the serum metabolic patterns, and to identify potential contributors to the formation of fatty liver and the correlated metabolic pathways. Relative to overfeeding for 7 days, a large number of endogenous molecules in serum of geese overfed for 25 days were altered. Continuous elevated levels of pyruvic acid, alanine, proline and beta-glycerophosphoric acid and reduced lactic acid level were observed in the serum of overfed geese. Pathway exploration found that the most of significantly different metabolites were involved in amino acids, carbohydrate and lipid metabolism. The present study exhibited the efficient capability of Landes geese to produce fatty liver, identified potential biomarkers and disturbed metabolic pathways in liver steatosis. These findings might reveal the underlying mechanisms of fatty liver formation and provide some theoretical basis for the diagnosis and treatment of liver diseases.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
W. A. García-Suástegui ◽  
L. A. Ramos-Chávez ◽  
M. Rubio-Osornio ◽  
M. Calvillo-Velasco ◽  
J. A. Atzin-Méndez ◽  
...  

Organisms have metabolic pathways that are responsible for removing toxic agents. We always associate the liver as the major organ responsible for detoxification of the body; however this process occurs in many tissues. In the same way, as in the liver, the brain expresses metabolic pathways associated with the elimination of xenobiotics. Besides the detoxifying role of CYP2E1 for compounds such as electrophilic agents, reactive oxygen species, free radical products, and the bioactivation of xenobiotics, CYP2E1 is also related in several diseases and pathophysiological conditions. In this review, we describe the presence of phase I monooxygenase CYP2E1 in regions of the brain. We also explore the conditions where protein, mRNA, and the activity of CYP2E1 are induced. Finally, we describe the relation of CYP2E1 in brain disorders, including the behavioral relations for alcohol consumption via CYP2E1 metabolism.


2021 ◽  
Vol 8 ◽  
Author(s):  
Fali Zhang ◽  
Peng Zhao ◽  
Zhongming Qian ◽  
Mingkang Zhong

It is known that lipopolysaccharide (LPS) triggers inflammatory response after intracerebroventricular (ICV) injection and elevates the expression of hepcidin through the interleukin 6/janus kinase 2/transducer and activator of the transcription 3 (IL-6/JAK2/STAT3) signaling pathway in the brain. This study was conducted to determine whether LPS ICV injection can regulate peripheral hepatic hepcidin expression and iron metabolism. Here, we studied the hepcidin expression in the liver, as well as serum iron and transferrin saturation, after LPS ICV injection. We also demonstrated the role of the IL-6/JAK2/STAT3 pathway in hepcidin expression in the livers of IL-6 knockout (IL-6–/– mice) and IL-6+/+ mice. AG490 was used to verify the effect of the IL-6/JAK2/STAT3 pathway on hepatic hepcidin expression. Our present study demonstrated that LPS ICV injection up-regulated hepatic hepcidin expression. This finding provides further evidence for highlighting the importance of the central inflammation on hepatic hepcidin expression and peripheral iron metabolism.


Author(s):  
Yujie Gong ◽  
Wentao Lyu ◽  
Xingfen Shi ◽  
Xiaoting Zou ◽  
Lizhi Lu ◽  
...  

Abstract Background:During the process of fatty liver production by overfeeding, the levels of endogenous metabolites in the serumof geese would change dramatically. This study investigated the effects of overfeeding on serum metabolism of Landes geese and the underlying mechanisms using a metabolomics approach.Results:Sixty Landes geese of the same age were randomly divided into the following 3 groups: D0 group (free from gavage); D7 group (overfeeding for 7 days); D25 group (overfeeding for 25 days). The results showed that overfeeding significantly increased the body weight and the liver weight of geese. Serum enzymatic activities and serum lipid levels were significantly enhanced following overfeeding.Gas chromatography time-of-flight/massspectrometry (GC-TOF/MS) was employed to explore the serum metabolic patterns, and to identify potential contributors to the formation of fatty liver and the correlatedmetabolic pathways. A large number of endogenous molecules in serum were altered, especially at the late stage of overfeeding (7 days to 25 days). Continuous elevated levels of pyruvic acid, alanine, proline and beta-glycerophosphoric acid and reduced lactic acid level were observed in the serum of overfed geese. Pathway exploration found that the most of significantly different metabolites were involved in various amino acids metabolism, carbohydrate metabolismand lipid metabolism.Conclusions: These findings pinpoint specific metabolite changes and identify potential biomarkers for early diagnosis of fatty liver disease, as well as provide insights into the perturbation of metabolic pathways involved in fatty liver formation.


Author(s):  
M.P. Sutunkova ◽  
B.A. Katsnelson ◽  
L.I. Privalova ◽  
S.N. Solovjeva ◽  
V.B. Gurvich ◽  
...  

We conducted a comparative assessment of the nickel oxide nanoparticles toxicity (NiO) of two sizes (11 and 25 nm) according to a number of indicators of the body state after repeated intraperitoneal injections of these particles suspensions. At equal mass doses, NiO nanoparticles have been found to cause various manifestations of systemic subchronic toxicity with a particularly pronounced effect on liver, kidney function, the body’s antioxidant system, lipid metabolism, white and red blood, redox metabolism, spleen damage, and some disorders of nervous activity allegedly related to the possibility of nickel penetration into the brain from the blood. The relationship between the diameter and toxicity of particles is ambiguous, which may be due to differences in toxicokinetics, which is controlled by both physiological mechanisms and direct penetration of nanoparticles through biological barriers and, finally, unequal solubility.


Author(s):  
Direnç Özlem Aksoy ◽  
Alpay Alkan

Background: Neurometabolic diseases are a group of diseases secondary to disorders in different metabolic pathways, which lead to white and/or gray matter of the brain involvement. </P><P> Discussion: Neurometabolic disorders are divided in two groups as dysmyelinating and demyelinating diseases. Because of wide spectrum of these disorders, there are many different classifications of neurometabolic diseases. We used the classification according to brain involvement areas. In radiological evaluation, MRI provides useful information for these disseases. Conclusion: Magnetic Resonance Spectroscopy (MRS) provides additional metabolic information for diagnosis and follow ups in childhood with neurometabolic diseases.


Parasitology ◽  
1941 ◽  
Vol 33 (4) ◽  
pp. 373-389 ◽  
Author(s):  
Gwendolen Rees

1. The structure of the proboscides of the larva of Dibothriorhynchus grossum (Rud.) is described. Each proboscis is provided with four sets of extrinsic muscles, and there is an anterior dorso-ventral muscle mass connected to all four proboscides.2. The musculature of the body and scolex is described.3. The nervous system consists of a brain, two lateral nerve cords, two outer and inner anterior nerves on each side, twenty-five pairs of bothridial nerves to each bothridium, four longitudinal bothridial nerves connecting these latter before their entry into the bothridia, four proboscis nerves arising from the brain, and a series of lateral nerves supplying the lateral regions of the body.4. The so-called ganglia contain no nerve cells, these are present only in the posterior median commissure which is therefore the nerve centre.


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