Protective effects of phyllanthin, a lignan from Phyllanthus amarus, against progression of high fat diet induced metabolic disturbances in mice

RSC Advances ◽  
2016 ◽  
Vol 6 (63) ◽  
pp. 58343-58353 ◽  
Author(s):  
Sneha Jagtap ◽  
Pragyanshu Khare ◽  
Priyanka Mangal ◽  
Kanthi Kiran Kondepudi ◽  
Mahendra Bishnoi ◽  
...  

Phyllanthin delayed the progression of high fat diet induced changes affecting lipid and glucose metabolism such as adiposity, hypertriglyceridemia, fatty liver, inflammation, lipid peroxidation and insulin resistance.

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Camila O. Souza ◽  
Alexandre A. S. Teixeira ◽  
Edson A. Lima ◽  
Helena A. P. Batatinha ◽  
Lara M. Gomes ◽  
...  

Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-αdependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF𝜅B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Caiping Lu ◽  
Hanying Xing ◽  
Linquan Yang ◽  
Kaiting Chen ◽  
Linyi Shu ◽  
...  

Diabetes mellitus is highly prevalent worldwide. High-fat-diet (HFD) consumption can lead to liver fat accumulation, impair hepatic glycometabolism, and cause insulin resistance and the development of diabetes. Resveratrol has been shown to improve the blood glucose concentration of diabetic mice, but its effect on the abnormal hepatic glycometabolism induced by HFD-feeding and the mechanism involved are unknown. In this study, we determined the effects of resveratrol on the insulin resistance of high-fat-diet-fed mice and a hepatocyte model by measuring serum biochemical indexes, key indicators of glycometabolism, glucose uptake, and glycogen synthesis in hepatocytes. We found that resveratrol treatment significantly ameliorated the HFD-induced abnormalities in glucose metabolism in mice, increased glucose absorption and glycogen synthesis, downregulated protein phosphatase 2A (PP2A) and activated Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ), and increased the phosphorylation of AMP-activated protein kinase (AMPK). In insulin-resistant HepG2 cells, the administration of a PP2A activator or CaMKKβ inhibitor attenuated the effects of resveratrol, but the administration of an AMPK inhibitor abolished the effects of resveratrol. Resveratrol significantly ameliorates abnormalities in glycometabolism induced by HFD-feeding and increases glucose uptake and glycogen synthesis in hepatocytes. These effects are mediated through the activation of AMPK by PP2A and CaMKKβ.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3338
Author(s):  
Hyeon A Lee ◽  
Jae-Han Cho ◽  
Qonita Afinanisa ◽  
Gi-Hong An ◽  
Jae-Gu Han ◽  
...  

Ganoderma lucidum is used widely in oriental medicine to treat obesity and metabolic diseases. Bioactive substances extracted from G. lucidum have been shown to ameliorate dyslipidemia, insulin resistance, and type 2 diabetes in mice via multiple 5′ AMP-activated protein kinase (AMPK)-mediated mechanisms; however, further studies are required to elucidate the anti-obesity effects of G. lucidum in vivo. In this study, we demonstrated that 3% G. lucidum extract powder (GEP) can be used to prevent obesity and insulin resistance in a mouse model. C57BL/6 mice were provided with a normal diet (ND) or a high-fat diet (HFD) supplemented with 1, 3, or 5% GEP for 12 weeks and the effect of GEP on body weight, liver, adipose tissue, adipokines, insulin and glucose tolerance (ITT and GTT), glucose uptake, glucose-metabolism related proteins, and lipogenesis related genes was examined. GEP administration was found to reduce weight gain in the liver and fat tissues of the mice. In addition, serum parameters were significantly lower in the 3% and 5% GEP mice groups than in those fed a HFD alone, whereas adiponectin levels were significantly higher. We also observed that GEP improved glucose metabolism, reduced lipid accumulation in the liver, and reduced adipocyte size. These effects may have been mediated by enhanced AMPK activation, which attenuated the transcription and translation of lipogenic genes such as fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1), and sterol regulatory element-binding protein-1c (SREBP1c). Moreover, AMP-activated protein kinase (AMPK) activation increased acetyl-CoA carboxylase (ACC), insulin receptor (IR), IR substrate 1 (IRS1), and Akt protein expression and activation, as well as glucose transporter type 1/4 (GLUT1/4) protein production, thereby improving insulin sensitivity and glucose metabolism. Together, these findings demonstrate that G. lucidum may effectively prevent obesity and suppress obesity-induced insulin resistance via AMPK activation.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1059
Author(s):  
Si Fan ◽  
Samnhita Raychaudhuri ◽  
Olivia Kraus ◽  
Md Shahinozzaman ◽  
Leila Lofti ◽  
...  

The shoot of Urtica dioica is used in several cultures as a vegetable or herb. However, not much has been studied about the potential of this plant when consumed as a whole food/vegetable rather than an extract for dietary supplements. In a 12-week dietary intervention study, we tested the effect of U. dioica vegetable on high fat diet induced obesity and insulin resistance in C57BL/6J mice. Mice were fed ad libitum with isocaloric diets containing 10% fat or 45% fat with or without U. dioica. The diet supplemented with U. dioica attenuated high fat diet induced weight gain (p < 0.005; n = 9), fat accumulation in adipose tissue (p < 0.005; n = 9), and whole-body insulin resistance (HOMA-IR index) (p < 0.001; n = 9). Analysis of gene expression in skeletal muscle showed no effect on the constituents of the insulin signaling pathway (AKT, IRS proteins, PI3K, GLUT4, and insulin receptor). Notable genes that impact lipid or glucose metabolism and whose expression was changed by U. dioica include fasting induced adipocyte factor (FIAF) in adipose and skeletal muscle, peroxisome proliferator-activated receptor-α (Ppar-α) and forkhead box protein (FOXO1) in muscle and liver, and Carnitine palmitoyltransferase I (Cpt1) in liver (p < 0.01). We conclude that U. dioica vegetable protects against diet induced obesity through mechanisms involving lipid accumulation and glucose metabolism in skeletal muscle, liver, and adipose tissue.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Bingxin Lu ◽  
Jianing Zhong ◽  
Jianfei Pan ◽  
Xiaopeng Yuan ◽  
Mingzhi Ren ◽  
...  

Abstract Background The growth differentiation factor 11 (GDF11) was shown to reverse age-related hypertrophy on cardiomyocytes and considered as anti-aging rejuvenation factor. The role of GDF11 in regulating metabolic homeostasis is unclear. In this study, we investigated the functions of GDF11 in regulating metabolic homeostasis and energy balance. Methods Using a hydrodynamic injection approach, plasmids carrying a mouse Gdf11 gene were delivered into mice and generated the sustained Gdf11 expression in the liver and its protein level in the blood. High fat diet (HFD)-induced obesity was employed to examine the impacts of Gdf11 gene transfer on HFD-induced adiposity, hyperglycemia, insulin resistance, and hepatic lipid accumulation. The impacts of GDF11 on metabolic homeostasis of obese and diabetic mice were examined using HFD-induced obese and STZ-induced diabetic models. Results Gdf11 gene transfer alleviates HFD-induced obesity, hyperglycemia, insulin resistance, and fatty liver development. In obese and STZ-induced diabetic mice, Gdf11 gene transfer restores glucose metabolism and improves insulin resistance. Mechanism study reveals that Gdf11 gene transfer increases the energy expenditure of mice, upregulates the expression of genes responsible for thermoregulation in brown adipose tissue, downregulates the expression of inflammatory genes in white adipose tissue and those involved in hepatic lipid and glucose metabolism. Overexpression of GDF11 also activates TGF-β/Smad2, PI3K/AKT/FoxO1, and AMPK signaling pathways in white adipose tissue. Conclusions These results demonstrate that GDF11 plays an important role in regulating metabolic homeostasis and energy balance and could be a target for pharmacological intervention to treat metabolic disease.


2018 ◽  
Vol 88 (5-6) ◽  
pp. 234-243
Author(s):  
Soo Im Chung ◽  
Catherine W. Rico ◽  
Sang Chul Lee ◽  
Mi Young Kang

Abstract. The effects of instant cooked rice made from a combination of white rice and pigmented giant embryonic Keunnunjami rice, in comparison with those of instant regular white or brown rice and instant non-pigmented giant embryonic brown rice, on the glucose metabolism and antioxidant defense status in high-fat diet-fed mice were investigated. 56 male C57BL/6N mice were randomly divided into 7 dietary groups: normal control, high fat (23 %, HF), and HF supplemented with normal white (HF + NW) or brown rice (HF + NB), non-pigmented giant embryonic rice (HF + GB), and white rice with 8 % Keunnunjami (HF + KJ8) and 18 % Keunnunjami (HF + KJ18). After 7 weeks, HF mice showed marked increases in blood glucose (156 mg/dL), plasma insulin (12.1 mg/mL), and lipid peroxidation, and a significant decrease in hepatic glycogen (14.2 mg/g) relative to the control group (p < 0.05). However, addition of instant NB, GB, KJ8, andKJ18) rice suppressed this high-fat diet-induced hyperglycemia and oxidative stress through altering glucose-regulating enzymes (glucokinase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase) and activation of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, glutathione reductase, and paraoxonase). Compared with HF mice, HF + KJ8 and HF + KJ18 groups exhibited significantly lower glucose (139–141 mg/dL), insulin (10.6–10.9 mg/mL), and lipid peroxidation and higher glycogen (15.3–16.4 mg/g) (p < 0.05). The hypoglycemic and antioxidant effects of instant KJ8 and KJ18 rice were generally comparable to those of instant NB and GB rice. These findings illustrate that instant rice made from white rice with 8 % Keunnunjami rice may be useful as a functional food with therapeutic potential against hyperglycemia and oxidative damage.


2016 ◽  
Vol 61 (3) ◽  
pp. 1600418 ◽  
Author(s):  
Adriano Lama ◽  
Claudio Pirozzi ◽  
Maria Pia Mollica ◽  
Giovanna Trinchese ◽  
Francesca Di Guida ◽  
...  

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5874
Author(s):  
Ewa Żary-Sikorska ◽  
Bartosz Fotschki ◽  
Adam Jurgoński ◽  
Monika Kosmala ◽  
Joanna Milala ◽  
...  

Due to the demonstrated intestinal microbial transformation of strawberry ellagitannins (ET) into bioactive metabolites, in the current study on rats, we hypothesised that the dietary addition of a strawberry ET-rich extract (S-ET) to a high-fat diet (HFD) would attenuate disturbances in the redox and lipid status as well as in the inflammatory response. We randomly distributed 48 Wistar rats into six groups and used two-way analysis of variance (ANOVA) to assess the effects of two main factors—diet type (standard and high-fat) and ET dosage (without, low, and 3× higher)—applied to rats for 4 weeks. In relation to the hypothesis, irrespective of the dosage, the dietary application of ET resulted in the desired attenuating effects in rats fed a HFD as manifested by decreased body weight gain, relative mass of the epididymal pad, hepatic fat, oxidized glutathione (GSSG), triglycerides (TG), total cholesterol (TC), and thiobarbituric acid-reactive substances (TBARS) concentrations as well as desired modifications in the blood plasma parameters. These beneficial changes were enhanced by the high dietary addition of ET, which was associated with considerably higher concentrations of ET metabolites in the urine and plasma of rats. The results indicated that S-ET could be effectively used for the prevention and treatment of metabolic disturbances associated with obesity, dyslipidaemia, redox status imbalance, and inflammation.


Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1241
Author(s):  
Patrycja Bielawiec ◽  
Ewa Harasim-Symbor ◽  
Karolina Konstantynowicz-Nowicka ◽  
Klaudia Sztolsztener ◽  
Adrian Chabowski

Numerous studies showed that sustained obesity results in accumulation of bioactive lipid derivatives in several tissues, including skeletal muscle, which further contributes to the development of metabolic disturbances and insulin resistance (IR). The latest data indicate that a potential factor regulating lipid and glucose metabolism is a phytocannabinoid—cannabidiol (CBD), a component of medical marijuana (Cannabis). Therefore, we aimed to investigate whether chronic CBD administration influences bioactive lipid content (e.g., ceramide (CER)), as well as glucose metabolism, in the red skeletal muscle (musculus gastrocnemius) with predominant oxidative metabolism. All experiments were conducted on an animal model of obesity, i.e., Wistar rats fed a high-fat diet (HFD) or standard rodent chow, and subsequently injected with CBD in a dose of 10 mg/kg or its solvent for two weeks. The sphingolipid content was assessed using high-performance liquid chromatography (HPLC), while, in order to determine insulin and glucose concentrations, immunoenzymatic and colorimetric methods were used. The protein expression from sphingolipid and insulin signaling pathways, as well as endocannabinoidome components, was evaluated by immunoblotting. Unexpectedly, our experimental model revealed that the significantly intensified intramuscular de novo CER synthesis pathway in the HFD group was attenuated by chronic CBD treatment. Additionally, due to CBD administration, the content of other sphingolipid derivatives, i.e., sphingosine-1-phosphate (S1P) was restored in the high-fat feeding state, which coincided with an improvement in skeletal muscle insulin signal transduction and glycogen recovery.


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