scholarly journals Maternal High-Fat Diet Alters the Characteristics of Astrocytes and Worsens the Outcome of Stroke in Rat Offspring, Which Improves After FGF21 Administration

Author(s):  
Yanxuan Li ◽  
Mengqi Lin ◽  
Ping Lin ◽  
Nengzhi Xia ◽  
Xiaokun Li ◽  
...  

Background: Maternal high-fat diet (MHFD) has been shown to increase susceptibility to neurological disease in later offspring, but the underlying mechanism is not clear. Fibroblast growth factor 21 (FGF21) has been reported to have a neuroprotective effect in stroke, but its mechanism of action remains unknown. In this study, we investigated the mechanism of the effect of MHFD on stroke in offspring in adulthood and the mechanism by which FGF21 acts on stroke and restores neurological function.Methods: We performed transcriptome sequencing analysis on D21 neonatal rats. Bodyweight and blood indicators were recorded in the adult rats after MHFD. FGF21 was administered 7 h after photochemical modeling twice a day for three consecutive days.Results: We found numerous mRNA changes between the MHFD group and a normal maternal normal diet (MND) group at D21, including genes related to astrocyte and PI3K/Akt pathways. The body weight, blood glucose, and triglycerides of the MHFD offspring were higher, ischemic lesions were larger, the number of activated astrocytes was lower, and the neurological function score was worse than that of the MND group. After FGF21 administration, WB and qPCR analyses showed that astrocytes and the PI3K/Akt pathway were upregulated, while NF-κB and inflammatory cytokines expression were inhibited in stroke and peri-stroke regions.Conclusion: Taken together, we conclude that MHFD alters the characteristics of astrocytes and other transcriptome changes in their offspring, leading to a worse prognosis of stroke, while FGF21 plays a neuroprotective role by inhibiting NF-κB and inflammatory factors and activating the PI3K/Akt pathway and activating more astrocytes in the MND group than the MHFD group.

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3438
Author(s):  
Maria Angela Guzzardi ◽  
Federica La Rosa ◽  
Daniela Campani ◽  
Andrea Cacciato Insilla ◽  
Vincenzo De Sena ◽  
...  

Metabolic-associated fatty liver disease is a major cause of chronic pathologies, of which maternal obesity is a frequent risk factor. Gut wall and microbiota, visceral fat, and liver form a pre-systemic network for substrates and pro-inflammatory factors entering the body, undergoing accelerated maturation in early-life when the weaning reaction, i.e., a transitory inflammatory condition, affects lifelong health. We aimed to characterize organ metabolism in the above network, in relation to weaning reaction and maternal obesity. Weaning or 6-months-old offspring of high-fat-diet and normal-diet fed dams underwent in vivo imaging of pre-/post-systemic glucose uptake and tissue radiodensity in the liver, visceral fat, and intestine, a liver histology, and microbiota and metabolic pathway analyses. Weaning mice showed the dominance of gut Clostridia and Bacteroidia members, overexpressing pathways of tissue replication and inflammation; adulthood increased proneness to steatohepatitis, and Desulfovibrio and RF39 bacteria, and lipopolysaccharide, bile acid, glycosaminoglycan, and sphingolipid metabolic pathways. In vivo imaging could track organ maturation, liver inflammation, and protective responses. A maternal high-fat diet amplified the weaning reaction, elevating liver glucose uptake, triglyceride levels, and steatohepatitis susceptibility along the lifespan. The visceral network establishes a balance between metabolism and inflammation, with clear imaging biomarkers, and crucial modulation in the weaning time window.


2021 ◽  
pp. 2100065
Author(s):  
Zhen Li ◽  
Viola J. Kosgei ◽  
Anais Bison ◽  
Jean‐Marc Alberto ◽  
Remi Umoret ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Souravh Bais ◽  
Guru Sewak Singh ◽  
Ramica Sharma

In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/dL) as well as changes in body temperature of animals. Treatment of obese rats with MEMOL for 49 days resulted in a significant (P<0.001) change in body weight, total cholesterol, triglycerides, and LDL level along with a significant (P<0.001) increase in body temperature as compared to the HFD-induced obesity. MEMOL treated rats also showed a significant decrease in the level of liver biomarkers, organ weight, and blood glucose level. Further, rats treated with MEMOL (200 mg and 400 mg/kg) show reduced atherogenic index (1.7 ± 0.6 and 0.87 ± 0.76). The results indicate that the rats treated with Moringa oleifera (MO) have significantly attenuated the body weight without any change in the feed intake and also elicited significant thermogenic effect and to act as hypolipidemic and thermogenic property in obesity related disorders.


2021 ◽  
Author(s):  
Sathish Sivaprakasam ◽  
Sabarish Ramachandran ◽  
Mohd Omar Faruk Sikder ◽  
Yangzom Doma Bhutia ◽  
Mitchell Wachtel ◽  
...  

a-Methyl-L-tryptophan (a-MLT) is currently in use as a tracer in its 11C-labeled form to monitor the health of serotonergic neurons in humans. In the present study, we found this compound to function as an effective weight-loss agent at pharmacological doses in multiple models of obesity in mice. The drug was able to reduce the body weight when given orally in drinking water (1 mg/ml) in three different models of obesity: normal mice on high-fat diet, Slc6a14-null mice on high-fat diet, and ob/ob mice on normal diet. Only the L-enantiomer (a-MLT) was active while the D-enantiomer (a-MDT) had negligible activity. The weight-loss effect was freely reversible, with the weight gain resuming soon after the withdrawal of the drug. All three models of obesity were associated with hyperglycemia, insulin resistance, and hepatic steatosis; a-MLT reversed these features. There was a decrease in food intake in the treatment group. Mice on a high-fat diet showed decreased cholesterol and protein in the serum when treated with a-MLT; there was however no evidence of liver and kidney dysfunction. Plasma amino acid profile indicated a significant decrease in the levels of specific amino acids, including tryptophan; but the levels of arginine were increased. We conclude that a-MLT is an effective, reversible, and orally active drug for the treatment of obesity and metabolic syndrome.


2013 ◽  
Vol 83 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Luciana Simão Carmo ◽  
Marcelo Macedo Rogero ◽  
Mayara Cortez ◽  
Monica Yamada ◽  
Patrícia Silva Jacob ◽  
...  

An excessive consumption of a high-fat diet (HFD) results in becoming overweight or obese, which triggers a chronic inflammatory condition that is associated with a high white blood cell count. Because of the potential for yerba maté (Ilex paraguariensis) (YM) to impact obesity, this study aimed to investigate the effects of YM consumption on the hematological response and on the production of interleukin (IL)-1α, IL-6, tumor necrosis factor (TNF)-α, and IL-10 by bone marrow cells from Wistar rats fed a HFD. Male Wistar rats were fed a control (CON) or HFD diet for twelve weeks. At the end of this period, the rats received YM (1 g/kg/day body weight) for 4 weeks. After euthanasia, hemograms and myelograms were evaluated, while the bone marrow cells were cultured in the presence or absence of lipopolysaccharide (LPS) to evaluate the production of IL-1α, IL-6, TNF-α, and IL-10. The consumption of YM reduced the body weight, the body adiposity, and the cholesterol levels in HFD-fed rats. Bone marrow cells from the HFD group produced more IL-1α, IL-6, and TNF-α, and less IL-10, when compared to cells from the control group, and YM consumption reduced the IL-1α, IL-6, and TNF-α production by the cells. However, cells from the HFD rats that were stimulated with LPS increased their IL-1α, IL-6, and TNF-α production, but YM consumption did not change this result. In summary, the consumption of YM affects the production of IL-1α, IL-6, and TNF-α by bone marrow cells, promotes weight loss, decreases the number of white blood cells, and significantly improves serum cholesterol level in HFD-fed rats. However, the bone marrow cells from the HFD+YM-fed rats challenged with LPS did not show improvement in the inflammatory response compared to the cells from animals fed only a HFD that were also challenged with LPS.


Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 99 ◽  
Author(s):  
Wang Ling ◽  
Shungeng Li ◽  
Xingcai Zhang ◽  
Yongquan Xu ◽  
Ying Gao ◽  
...  

: Probiotic dark tea (PDT) is a novel kind of dark tea produced by fresh albino tea leaves and fermented with specific probiotics. Our study demonstrates that PDT can ameliorate high-fat diet-induced overweight and lipid metabolic disorders and shows no acute or subacute toxicity in Sprague-Dawley (SD) rats. Daily intragastric administration of 5% PDT infusion for 14 days caused no obvious effect on general physiological features and behaviors of rats. Oral administration of 1%, 2%, and 3% of PDT infusion for six weeks had no influence on the biochemistry and histopathology of rats’ organs and blood, as well as the body weight and ratios of organ/body weight. To investigate its anti-obesity activity, SD rats were randomly divided into four groups, treated with normal diet + water (Group I), high-fat diet + water (Group II), high-fat diet + 3% traditional dark tea infusion (Group III), high-fat diet + 3% PDT infusion (Group IV). After six weeks, the body weight, serum total triacylglycerol (TG) and serum total cholesterol (TC) levels of rats in Group II were significantly increased and the high-density lipoprotein cholesterol (HDL) levels were significantly decreased compared with those in the other three groups. Both traditional dark tea and PDT treatment effectively counteracted the adverse effect of a high-fat diet in SD rats. These results suggest that PDT could be applied for the prevention of obesity, which ameliorates overweight and lipid metabolic disorders and which shows no acute or subacute toxicity.


Abstract Background and aims The prevalence of non-alcoholic fatty liver disease has been alarmingly increased with no lines of effective treatment. Vanillic acid is a naturally occurring polyphenol with promising therapeutic effects. Exercise is well known to be an effective tool against obesity and its consequences. Thus, we aim to study the effect of vanillic acid alone and along with exercise on fatty liver induced by a high-fat diet in a rat model and to investigate possible novel mechanisms involved in their action. Methods In this study, 40 male rats were divided equally into five groups: control (standard chow diet), HFD (high-fat diet), HFD+VA (HFD+ vanillic acid (50 mg/kg/day orally), HFD+EX (HFD+ swimming exercise 5 days/week), HFD+VA+EX (HFD+ vanillic acid+ swimming exercise) for eight weeks. Results Body mass, liver weight, liver enzymes, cholesterol, and triglycerides were significantly decreased in the combined VA+EX group, with marked improvement in hyperglycemia, hyperinsulinemia, and consequently HOMA-IR index compared to the HFD group. These improvements were also reflected in the pathological view. VA and swimming, either solely or in combination, markedly increased hepatic and circulating fibroblast growth factor 21. Additionally, VA and swimming increased the immunohistochemical expression of the autophagosomal marker LC3 and decreased the expression of P62, which is selectively degraded during autophagy. Conclusions These results suggest the hepatoprotective effect of VA and swimming exercise against fatty liver and the involvement of FGF21 and autophagy in their effect.


2020 ◽  
Author(s):  
Xiaoling Wu ◽  
Xinyu Zou ◽  
Mi Zhang ◽  
Haiqiang Hu ◽  
Xueliang Wei ◽  
...  

Abstract Background: Osteocalcin (OCN), as an energy-regulating hormone, involves in preventing nonalcoholic steatohepatitis. Laying hens have been used as an animal model for investigating liver function and related metabolic disordersas that the synthesis of fat in laying hens is much faster than in mammals with limited adipose tissue. The aim of this study was to investigate the effects of OCN on fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Methods: Thirty 68-week-old White Plymouth laying hens were randomly assigned into conventional single-bird cages, and the cages were randomly allocated into one of three treatments: normal diet (ND + vehicle , ND+V), high-fat diet (HFD + vehicle, HFD+V), and HFD + OCN (3 μg/bird, 1 time/2 days, i.m.) for 40 days. At experimental day 30, oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) were performed. At the end of experiment, the hens were euthanized followed blood collection. The plasma aspartate transaminase (AST), alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automatic biochemistry analyzer. Pathological changes in the liver were examined under both light and transmission electron microscopes. The plasma inflammatory factors including interleukin-1 (IL-1), IL-6, and tumor Necrosis Factor-alpha (TNF-α) were analyzed by ELISA, and the gene expressions of these inflammatory factors in the liver were analyzed by Real-time PCR. And oxidative stress was evaluated using Malondialdehyde (MDA) and Glutathione peroxidase (GSH-Px) assay kits. Results: The results showed HFD hens had more severe liver haemorrhage and fibrosis than ND hens. The ultra-microstructural examination showed that hepatocytes of HFD hens appeared necrotic pyknosis associated with great intracellular electron, mitochondrial swelling, shrunk nucleus and absence of autolysosomes. OCN mitigated these pathological changes by improved HFD hens’ insulin resistance via alleviating the glucose intolerence and improving insulin sensitivity; inhibited HFD-induced oxidative stress as evidenced by decreased liver concentrations of MDA but increased GSH-Px; and reduced the inflammatory reaction with reducing blood IL-6 and TNF-α concentrations and mRNA expressions. Conclusion: These results suggest a high-fat diet promotes the FLHS development in aged hens, while OCN prevents the FLHS process through inhibiting insulin resistance, inflammatory reaction, oxidative stress and fibrosis, and acting autophagy.


2019 ◽  
Vol 122 (9) ◽  
pp. 1062-1072 ◽  
Author(s):  
Jian Sang ◽  
Hengxian Qu ◽  
Ruixia Gu ◽  
Dawei Chen ◽  
Xia Chen ◽  
...  

AbstractExcessive intake of high-energy diets is an important cause of most obesity. The intervention of rats with high-fat diet can replicate the ideal animal model for studying the occurrence of human nutritional obesity. Proteomics and bioinformatics analyses can help us to systematically and comprehensively study the effect of high-fat diet on rat liver. In the present study, 4056 proteins were identified in rat liver by using tandem mass tag. A total of 198 proteins were significantly changed, of which 103 were significantly up-regulated and ninety-five were significantly down-regulated. These significant differentially expressed proteins are primarily involved in lipid metabolism and glucose metabolism processes. The intake of a high-fat diet forces the body to maintain physiological balance by regulating these key protein spots to inhibit fatty acid synthesis, promote fatty acid oxidation and accelerate fatty acid degradation. The present study enriches our understanding of metabolic disorders induced by high-fat diets at the protein level.


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