Effect of succinic acid on the organism of mice and their intestinal microbiota against the background of excessive fat consumption

Succinic acid and its salts (succinates) positively affect the oxygenation of the internal environment, stabilize the structure and functional activity of mitochondria, and normalize the ion metabolism in the cell. Separate clinical studies and experimental surveys confirmed that having low toxicity succinic acid has well-manifested antioxidant, immunostimulating, adaptogenic properties. In this study, we determined the influence of succinic acid on the organism of laboratory animals against the backround of high-fat diet: the changes in body weight, indices of the mass of the internal organs, blood parameters and the changes in the intestinal microbiota were determined. For the experiment, we formed three experimental and three control groups of male white mice. The animals of the control group received 0.5% solution of succinic acid instead of water. In the experiment, we determined that succinic acid has no effect on the intensity of growth of weight of young mice against the background of excessive fat in their diet. Excessive consumption of fat by male mice leads to mainly disorders in the functioning of the liver, excretory and the immune systems. High-fat diet of mice is accompanied by impaired hepatic function, manifested in sharp hypoproteinemia due to globulins, increase in the activity of hepatic enzymes against the background of reduced activity of alkaline phosphatase, increase in the level of bilirubin, and decrease in glucose. Excess of fat in the diet leads to malfunctioning of the excretory system, manifested in the reduced index of kidneys’ weight, high content of creatinine and reduced level of urea in the blood. Addition of succinic acid has a positive effect on the functional condition of the liver and the kidneys, especially noticeable during long-term intake. High-fat diet causes disorders in the functioning of the organs of blood circulation and immune protection, accompanied by decrease in the relative mass of the thymus and spleen, low content of hemoglobin and the number of erythrocytes, but has no significant effect on the content of other cellular elements in the blood. By the middle of the experiment, succinic acid had exacerbated these processes compared to the control, but by the end of the experiment, by contrast, these processes were alleviated. Addition of the succinic acid to high-fat diet contributed to the change in the quantitative composition of the main representatives of the obligatory microbiota (Bifidobacterium spp., Lactobacillus spp. and typical Escherichia coli) in the laboratory animals. Such changes in the intestinal microbiota may lead to such consequences as reproduction of the facultative microflora, and, thus, development of various diseases.

Download Full-text

Impact of a High-fat Diet on the Development of Chronic Inflammation in Heart of Wistar rats

Folia Medica ◽

10.3897/folmed.61.e39348 ◽

2019 ◽

Vol 61 (3) ◽

pp. 404-410

Author(s):

Iliyan V. Dimitrov ◽

Vassil I. Kamenov ◽

Nikolay P. Boyadjiev ◽

Katerina N. Georgieva ◽

Anelia V. Bivolarska ◽

...

Keyword(s):

Chronic Inflammation ◽

High Fat Diet ◽

Wistar Rats ◽

Interleukin 4 ◽

Laboratory Animals ◽

Control Group ◽

Low Grade ◽

High Fat ◽

Amyloid A ◽

Anti Inflammatory

Introduction: Obesity is linked to the development of low-grade, chronic inflammation. Obesity-related inflammation appears to be a different type of inflammation, mainly due to excessive food intake and unusual homeostasis. It can be evaluated by measuring the concentration of pro- and anti-inflammatory marker molecules – C-reactive protein (CRP), serum amyloid-A (SAA) and interleukin-4. Aim: The aim of the present study is to evaluate the rate of the inflammatory process in heart, provoked by the consumption of a high-fat diet. Materials and methods: Sixty 8-week-old male Wistar rats were used in this experiment. The laboratory animals were fed orally with two different types of rodent food for 14 or 18 weeks – a high-fat diet (experimental groups) and standard rodent food (control groups). They all were kept under standard housing conditions. The levels of the pro- and anti-inflammatory markers in tissue homogenates from heart were analyzed using ELISA. Their expression in tissue samples was detected immunohistochemically by the biotin-streptavidin-peroxidase method. The total protein concentration was determined by the Lawry method. Results: CRP levels showed no significant differences when the control group was compared with the groups fed with a high-fat diet (p>0.05). The SAA levels detected were also insignificantly changed. Only the IL-4 tissue levels showed tendency to increase (p<0.05) in the high-fat diet group. Conclusions: Our experiment indicates that there is a specific reaction of the heart to a high-fat diet. It also refers to the existence of adaptive mechanisms allowing the heart to counteract the development of dietary induced inflammation.

Download Full-text

Effect of Duyun Compound Green Tea on Gut Microbiota Diversity in High-Fat-Diet-Induced Mice Revealed by Illumina High-Throughput Sequencing

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8832554 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Caibi Zhou ◽

Xiaolu Zhou ◽

Zhirui Wen ◽

Zaibo Yang ◽

Ren Mu ◽

...

Keyword(s):

Treatment Group ◽

Green Tea ◽

Intestinal Microbiota ◽

High Throughput ◽

High Fat Diet ◽

Intestinal Tract ◽

High Throughput Sequencing ◽

Control Group ◽

High Fat ◽

Beneficial Bacteria

Intake of a high-fat diet (HFD) is closely related to disorders of the intestinal microbiota, which plays a key role in the pathogenesis of obesity. Duyun compound green tea, an ancient Chinese drink, is widely consumed to reduce weight, although the mechanism is not clear. In this study, 50 mice were randomly divided into 5 groups: normal control group (CK), HFD model control group (NK), positive control group with medicine (YK), low-dose compound tea group (DL), and high-dose compound tea group (DH). After 4 weeks of intervention, the feces of mice were taken under sterile conditions and evaluated using Illumina high-throughput sequencing technology. The results showed that the diversity of intestinal microbiota was the highest in the CK group, the lowest in the NK group, and relatively increased in the compound tea treatment group. Second, there were differences in intestinal microbiota in each group, among which the beneficial bacteria in the intestinal tract of the CK group were higher than those in the other groups, while the beneficial bacteria in each compound tea treatment group were more abundant than those in the NK group, in which harmful bacteria in the intestinal tract were found to be the highest. These results suggest that compounds in tea may be able to attenuate imbalances of intestinal microbiota induced by poor diet, acting as a therapeutic agent in obesity or other diseases associated with gut dysbiosis.

Download Full-text

A potential probiotic- Lachnospiraceae NK4A136 group: Evidence from the restoration of the dietary pattern from a high-fat diet

10.21203/rs.3.rs-48913/v1 ◽

2020 ◽

Author(s):

Menq-Rong Wu ◽

Te-Sen Chou ◽

Ching-Ying Huang ◽

Jong-Kai Hsiao

Keyword(s):

Dietary Pattern ◽

High Fat Diet ◽

Blood Lipid ◽

Hepatic Function ◽

Physiological Parameters ◽

Control Group ◽

Chow Diet ◽

High Fat ◽

Short Term ◽

Dietary Shift

Abstract Background: High-fat diet (HFD) that contributes to obesity is one of the pivotal risk factors for metabolic syndrome and cancers. The dietary pattern can shape the intestinal bacterial community and influence the physiological parameters. This study aimed to investigate whether the short-term dietary pattern shift from HFD to a balanced chow diet (CD) could correct HFD-induced colonic dysbiosis and reverse adverse health effects and identify the specific bacteria that changed by dietary patterns. Results: C57BL/6 mice fed with an HFD for 10 months, followed by a CD for 3 months, served as the dietary shift model. Stool samples were collected for bacterial analysis. Physiological parameters, such as serum adipokines, blood lipid levels, and hepatic function, were monitored in control and dietary shift groups. HFD-induced weight gain was mitigated by the dietary shift. A highly similar structure at the phylum, genus, and species levels was observed in the beta diversity of colonic bacteria in mice that underwent the dietary shift as compared to those in the control group. Notably, the abundance of Peptococcaceae and Akkermansiaceae in HFD-fed mice reduced after the dietary shift; whereas the diminished amount of probiotic Lachnospiraceae NK4A136 group in HFD-fed mice was restored to the level comparable to those in controls after the dietary shift. Conclusions: Our finding suggests that a dietary switch from a long-term HFD to a short-term balanced diet has the potential to correct colonic dysbiosis and restore physiological homeostasis. The Lachnospiraceae NK4A136 group has the potential to be a probiotic.

Download Full-text

Intestinal Microbiota Mediates High-Fructose and High-Fat Diets to Induce Chronic Intestinal Inflammation

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.654074 ◽

2021 ◽

Vol 11 ◽

Author(s):

Rong Tan ◽

Huiwei Dong ◽

Zhengshan Chen ◽

Min Jin ◽

Jing Yin ◽

...

Keyword(s):

Intestinal Microbiota ◽

High Fat Diet ◽

Intestinal Inflammation ◽

Control Group ◽

High Fat ◽

Microbial Composition ◽

High Fructose ◽

High Fat Diets ◽

Fat Diets ◽

Chronic Intestinal Inflammation

An unhealthy diet has been linked to increased incidence of chronic diseases. To investigate the relationship between diet and intestinal inflammation, mice in two experimental groups were fed on a high-fat diet or high-fructose diet, respectively. The result showed that the defecation volume of the experimental groups was significantly reduced compared with that of the control group, and the levels of pro-inflammatory cytokines (interleukin (IL)-1β and IL-6) and IgG in serum were increased significantly. In addition, inflammatory cell infiltration was observed in intestinal tissue, indicating that a high-fructose or high-fat diet can lead to constipation and inflammation. Further analysis showed that the microbial composition of the experimental groups changed significantly, including a decrease of the Bacteroidetes/Firmicutes ratio and increased levels of Bacteroides, Akkermansia, Lactobacillus, and Ruminococcus, which might be associated with inflammation. The results of pro-inflammatory metabolites analysis showed that the levels of arachidonic acid, stearic acid, and indoxylsulfuric acid were significantly increased in the experimental groups, which were related significantly to Bacteroides, Enterococcus, and Akkermansia. Meanwhile, the content of 5-hydroxytryptamine (5-HT) was significantly decreased, which might cause constipation by reducing intestinal peristalsis. Moreover, transplantation of fecal bacteria from inflammatory mice caused constipation and inflammation in normal mice, which could be relieved by feeding a normal diet. The results of the present study indicated that changes in intestinal microbiota and microbial metabolites may underlie chronic intestinal inflammation and constipation caused by high-fructose and high-fat diets.

Download Full-text

Anti-Obesity and Hypocholesterolemic Actions of Protamine-Derived Peptide RPR (Arg-Pro-Arg) and Protamine in High-Fat Diet-Induced C57BL/6J Mice

Nutrients ◽

10.3390/nu13082501 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2501

Author(s):

Maihemuti Mijiti ◽

Ryosuke Mori ◽

Bingyu Huang ◽

Kenichiro Tsukamoto ◽

Keisuke Kiriyama ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Fecal Excretion ◽

Control Group ◽

High Fat ◽

Tissue Weight ◽

Cholesterol Levels ◽

Adipose Tissue Weight ◽

Fas Mrna ◽

Hypocholesterolemic Peptide

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.

Download Full-text

Repercussion of Maternal Diabetes and Post-Weaning High-Fat Diet Consumption in Laboratory Animals

Metabolism ◽

10.1016/j.metabol.2020.154652 ◽

2021 ◽

Vol 116 ◽

pp. 154652

Author(s):

Veronyca G. Paula ◽

Yuri K. Sinzato ◽

Rafaianne Q.M. Souza ◽

Larissa L. Cruz ◽

Eduardo Kloppel ◽

...

Keyword(s):

High Fat Diet ◽

Maternal Diabetes ◽

Laboratory Animals ◽

High Fat

Download Full-text

Maternal tadalafil therapy for fetal growth restriction prevents non-alcoholic fatty liver disease and adipocyte hypertrophy in the offspring

Scientific Reports ◽

10.1038/s41598-020-80643-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Takuya Kawamura ◽

Hiroaki Tanaka ◽

Ryota Tachibana ◽

Kento Yoshikawa ◽

Shintaro Maki ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fetal Growth ◽

Fetal Programming ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Control Group ◽

High Fat ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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.

Download Full-text

Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice

Molecules ◽

10.3390/molecules26020302 ◽

2021 ◽

Vol 26 (2) ◽

pp. 302

Author(s):

Ahtesham Hussain ◽

Jin Sook Cho ◽

Jong-Seok Kim ◽

Young Ik Lee

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Mouse Model ◽

High Fat Diet ◽

Liver Diseases ◽

Liver Weight ◽

Control Group ◽

High Fat ◽

Herbal Formulation ◽

Plants Extract

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.

Download Full-text

High-fat diet-induced obesity and impairment of brain neurotransmitter pool

Translational Neuroscience ◽

10.1515/tnsci-2020-0099 ◽

2020 ◽

Vol 11 (1) ◽

pp. 147-160

Author(s):

Ranyah Shaker M. Labban ◽

Hanan Alfawaz ◽

Ahmed T. Almnaizel ◽

Wail M. Hassan ◽

Ramesa Shafi Bhat ◽

...

Keyword(s):

Oxidative Stress ◽

Brain Tissue ◽

High Fat Diet ◽

Density Lipoprotein ◽

Obese Group ◽

Control Group ◽

High Fat ◽

Brain Neurotransmitter ◽

The Brain ◽

Lean Group

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.

Download Full-text