Adzuki Bean Alleviates Obesity and Insulin Resistance Induced by a High-Fat Diet and Modulates Gut Microbiota in Mice

Adzuki bean consumption has many health benefits, but its effects on obesity and regulating gut microbiota imbalances induced by a high-fat diet (HFD) have not been thoroughly studied. Mice were fed a low-fat diet, a HFD, and a HFD supplemented with 15% adzuki bean (HFD-AB) for 12 weeks. Adzuki bean supplementation significantly reduced obesity, lipid accumulation, and serum lipid and lipopolysaccharide (LPS) levels induced by HFD. It also mitigated liver function damage and hepatic steatosis. In particular, adzuki bean supplementation improved glucose homeostasis by increasing insulin sensitivity. In addition, it significantly reversed HFD-induced gut microbiota imbalances. Adzuki bean significantly reduced the ratio of Firmicutes/Bacteroidetes (F/B); enriched the occurrence of Bifidobacterium, Prevotellaceae, Ruminococcus_1, norank_f_Muribaculaceae, Alloprevotella, Muribaculum, Turicibacter, Lachnospiraceae_NK4A136_group, and Lachnoclostridium; and returned HFD-dependent taxa (Desulfovibrionaceae, Bilophila, Ruminiclostridium_9, Blautia, and Ruminiclostridium) back to normal status. PICRUSt2 analysis showed that the changes in gut microbiota induced by adzuki bean supplementation may be associated with the metabolism of carbohydrates, lipids, sulfur, and cysteine and methionine; and LPS biosynthesis; and valine, leucine, and isoleucine degradation.

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Metformin alleviates insulin resistance in obese-induced mice via remodeling gut microbiota and intestinal metabolites

10.1101/2020.05.26.116715 ◽

2020 ◽

Author(s):

Ya Zhang ◽

Yang Cheng ◽

Jihui Zuo ◽

Liping Yan ◽

Qiaojuan Li ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Insulin Sensitivity ◽

Gut Microbiota ◽

High Fat Diet ◽

Underlying Mechanism ◽

Liver Inflammation ◽

High Fat ◽

Intracellular Ros ◽

And Oxidative Stress

AbstractMetformin is widely used to surmount insulin resistance (IR) and diabetes. Evidence indicates that metformin remodels gut microbiota but the underlying mechanism remain unclear. Present results showed that metformin effectively improved insulin sensitivity and alleviated liver inflammation and oxidative stress in high fat diet (HFD)-induced mice. Metabolomics analysis showed that metformin increased tauroursodeoxycholic acid (TUDCA) production by increasing the expression of bile acid synthase Cyp7a1 and Baat. In the palmitic acid (PA)-induced cell, TUDCA activated Nrf2/ARE pathway, thereby reducing intracellular ROS and improving insulin signaling. Further gut microbiota analysis showed that metformin increased the proportion of Akkermanisia muciniphlia in the HFD-fed mice, while TUDCA promoted the proliferation of A. muciniphlia but metformin did not. These findings reveal that metformin remodels the gut microbiota, reduces oxidative stress and enhances insulin sensitivity by increasing the production of TUDCA. This provides a novel mechanism by which metformin alleviates diet-induced IR and improves metabolism.

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Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

Food & Function ◽

10.1039/d1fo01394g ◽

2021 ◽

Author(s):

Haizhao Song ◽

Xinchun Shen ◽

Yang Zhou ◽

Xiaodong Zheng

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Gut Microbiota ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Liver Steatosis ◽

Obese Mice ◽

Black Rice ◽

High Fat ◽

Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

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SERUM LIPID PROFILE;

The Professional Medical Journal ◽

10.29309/tpmj/2008.15.04.2863 ◽

2008 ◽

Vol 15 (04) ◽

pp. 500-507

Author(s):

MUHAMMAD ANWAR BURIRO ◽

MUHAMMAD TAYYAB

Keyword(s):

Sunflower Oil ◽

High Fat Diet ◽

Serum Lipid ◽

Nigella Sativa ◽

Albino Rats ◽

High Fat ◽

Low Fat ◽

Control Groups ◽

Low Fat Diet ◽

Lipid Fractions

Objective: To determine the effects of Nigella sativa and sunflower oil diet intake on serum lipid profile in albino rats. Material& Methods: Eighty four albino rats with equal number of males and females were selected for the study, they were divided into six differentgroups, Control groups1,111,V,were given low fat diet(3%),high fat diet(20%), high fat diet supplemented with bile salt (1% colic acid) andantithyroid drug (0.5% propylthiouracil). The Experimental groups were given the above diets with supplemented Nigella sativa. Low fat dietincreased all the lipid fractions significantly when given at12 and 24 weeks duration as compared to 0 week. Results: The high fat diet whengiven at different intervals decreased all lipid fractions significantly as compared to baseline level. The high fat diet with propylthiouracil andbile salt also increased all the lipid fractions and the increase was more as compared to previous groups. The supplements of Nigella sativain the groups decreased all the lipid fractions significantly as compared to the control groups except HDL-c, which was significantly increasedin all the experimental groups as compared to control groups. Conclusion: On the basis of these findings conclusions are made, that Nigellasativa has got TG,TC, and LDL-c lowering and HDL-c raising effects.3% sunflower oil low fat diet has got TG,TC,HDL-c, and LDL-c raisingeffects.20% sunflower oil high fat diet has got TG,TC,HDL-c and LDL-c lowering effects. Both Nigella sativa and sunflower oil have got lowatherogenic index (TC/HDL) and may be recommended in hyperlipidaemic patients or normal individuals.

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CaMKIV limits metabolic damage through induction of hepatic autophagy by CREB in obese mice

Journal of Endocrinology ◽

10.1530/joe-19-0251 ◽

2020 ◽

Vol 244 (2) ◽

pp. 353-367 ◽

Cited By ~ 2

Author(s):

Jiali Liu ◽

Yue Li ◽

Xiaoyan Zhou ◽

Xi Zhang ◽

Hao Meng ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Inflammatory Response ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

Insulin Action ◽

Hepatic Insulin Resistance ◽

Obese Mice ◽

High Fat ◽

Impaired Insulin

High-fat diet (HFD) not only induces insulin resistance in liver, but also causes autophagic imbalance and metabolic disorders, increases chronic inflammatory response and induces mitochondrial dysfunction. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has recently emerged as an important regulator of glucose metabolism and skeletal muscle insulin action. Its activation has been involved in the improvement of hepatic and adipose insulin action. But the underlying mechanism is not fully understood. In the present study, we aimed to address the direct effects of CaMKIV in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. Our results indicated obese mice receiving CaMKIV showed decreased blood glucose and serum insulin and improved insulin sensitivity as well as increased glucose tolerance compared with vehicle injection. Meanwhile, defective hepatic autophagy activity, impaired insulin signaling, increased inflammatory response and mitochondrial dysfunction in liver tissues which are induced by high-fat diet were also effectively alleviated by injection of CaMKIV. Consistent with these results, the addition of CaMKIV to the culture medium of BNL cl.2 hepatocytes markedly restored palmitate-induced hepatic insulin resistance and autophagic imbalance. These effects were nullified by blockade of cyclic AMP response element-binding protein (CREB), indicating the causative role of CREB in action of CaMKIV. Our findings suggested that CaMKIV restores hepatic autophagic imbalance and improves impaired insulin sensitivity via phosphorylated CREB signaling pathway, which may offer novel opportunities for treatment of obesity and diabetes.

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Administration of Exogenous Melatonin Improves the Diurnal Rhythms of the Gut Microbiota in Mice Fed a High-Fat Diet

mSystems ◽

10.1128/msystems.00002-20 ◽

2020 ◽

Vol 5 (3) ◽

Cited By ~ 9

Author(s):

Jie Yin ◽

Yuying Li ◽

Hui Han ◽

Jie Ma ◽

Gang Liu ◽

...

Keyword(s):

Lipid Metabolism ◽

Gut Microbiota ◽

Circadian Clock ◽

High Fat Diet ◽

Serum Lipid ◽

Clock Genes ◽

Diurnal Rhythms ◽

High Fat ◽

Exogenous Melatonin ◽

Circadian Clock Genes

ABSTRACT Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in mice fed a high-fat diet (HFD) is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for 2 weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TG) showed a marked rhythm in the control in melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with that in the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rRNA gene sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes that correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but a nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of some specific gut microbiota in HFD-fed mice. IMPORTANCE The gut microbiota is strongly shaped by a high-fat diet, and obese humans and animals are characterized by low gut microbial diversity and impaired gut microbiota compositions. Comprehensive data on mammalian gut metagenomes shows gut microbiota exhibit circadian rhythms, which is disturbed by a high-fat diet. On the other hand, melatonin is a natural and ubiquitous molecule showing multiple mechanisms of regulating the circadian clock and lipid metabolism, while the role of melatonin in the regulation of the diurnal patterns of gut microbial structure and function in obese animals is not yet known. This study delineates an intricate picture of melatonin-gut microbiota circadian rhythms and may provide insight for obesity intervention.

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Selenoprotein W deficiency does not affect oxidative stress and insulin sensitivity in the skeletal muscle of high-fat diet-fed obese mice

AJP Cell Physiology ◽

10.1152/ajpcell.00064.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. C1172-C1182 ◽

Cited By ~ 3

Author(s):

Min-Gyeong Shin ◽

Hye-Na Cha ◽

Soyoung Park ◽

Yong-Woon Kim ◽

Jong-Yeon Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

High Fat Diet ◽

Control Diet ◽

In Vivo Studies ◽

Selenoprotein W ◽

Obese Mice ◽

High Fat

Selenoprotein W (SelW) is a selenium-containing protein with a redox motif found abundantly in the skeletal muscle of rodents. Previous in vitro studies suggest that SelW plays an antioxidant role; however, relatively few in vivo studies have addressed the antioxidant role of SelW. Since oxidative stress is a causative factor for the development of insulin resistance in obese subjects, we hypothesized that if SelW plays a role as an antioxidant, SelW deficiency could aggravate the oxidative stress and insulin resistance caused by a high-fat diet. SelW deficiency did not affect insulin sensitivity and H2O2 levels in the skeletal muscle of control diet-fed mice. SelW levels in the skeletal muscle were decreased by high-fat diet feeding for 12 wk. High-fat diet induced obesity and insulin resistance and increased the levels of H2O2 and oxidative stress makers, which were not affected by SelW deficiency. High-fat diet feeding increased the expression of antioxidant enzymes; however, SelW deficiency did not affect the expression levels of antioxidants. These results suggest that SelW does not play a protective role against oxidative stress and insulin resistance in the skeletal muscle of high-fat diet-fed obese mice.

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Liraglutide Increases FGF-21 Activity and Insulin Sensitivity in High Fat Diet and Adiponectin Knockdown Induced Insulin Resistance

PLoS ONE ◽

10.1371/journal.pone.0048392 ◽

2012 ◽

Vol 7 (11) ◽

pp. e48392 ◽

Cited By ~ 27

Author(s):

Mengliu Yang ◽

Lili Zhang ◽

Chong Wang ◽

Hua Liu ◽

Guenther Boden ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

High Fat Diet ◽

High Fat

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Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00465.2013 ◽

2014 ◽

Vol 307 (3) ◽

pp. R332-R339 ◽

Cited By ~ 8

Author(s):

Jieyun Yin ◽

Jian Kuang ◽

Manisha Chandalia ◽

Demidmaa Tuvdendorj ◽

Batbayar Tumurbaatar ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acid ◽

Blood Glucose ◽

Insulin Sensitivity ◽

Free Fatty Acid ◽

Glucose Tolerance ◽

High Fat Diet ◽

Postprandial Glucose ◽

Tolerance Test ◽

High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

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Whole body insulin sensitivity in Osborne-Mendel and S 5B/Pl rats eating a low- or high-fat diet

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.4.r785 ◽

1992 ◽

Vol 263 (4) ◽

pp. R785-R789 ◽

Cited By ~ 4

Author(s):

T. A. Buchanan ◽

J. S. Fisler ◽

S. Underberger ◽

G. F. Sipos ◽

G. A. Bray

Keyword(s):

Insulin Sensitivity ◽

High Fat Diet ◽

Whole Body ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

High Fat Diets ◽

Glucose Clearance ◽

Fat Diets ◽

Fat Feeding

To determine whether whole body insulin sensitivity differs between a rat strain that does not (S 5B/Pl) and a strain that does [Osborne-Mendel (OM)] become obese when eating a high-fat diet, we performed euglycemic clamp studies in animals from each strain during low- and high-fat feeding. Clamps were performed after 2 days ("initial clamp") and 9 days ("final clamp") on each diet. Plasma glucose and insulin levels during the final 60 min of initial and final clamps were similar in S 5B/Pl and OM rats regardless of diet. Insulin sensitivity, measured as the glucose clearance rate during the final 60 min of the clamp, averaged 35 +/- 3 ml.kg-1.min-1 in S 5B/Pl rats after 2 days on a low-fat diet. This did not change significantly during an additional 7 days on the low-fat diet. The high-fat diet was associated with a 13% reduction in insulin sensitivity after 2 days and a 30% reduction after 9 days in S 5B/Pl rats. OM rats exhibited similar patterns of insulin sensitivity during low- and high-fat diets, albeit at lower insulin sensitivity overall (P < 0.0005 vs. S 5B/Pl). Mean glucose clearance after 2 days on the low-fat diet was 27 +/- 2 mg.kg-1.min-1 and did not change significantly during seven more days of low-fat feeding. The high-fat diet was associated with a 19% reduction in glucose clearance after 2 days and a 38% reduction after 9 days in OM rats. The magnitude of reduction in insulin sensitivity during high-fat diets did not differ significantly between strains.(ABSTRACT TRUNCATED AT 250 WORDS)

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Oleacein Prevents High Fat Diet-Induced A Diposity and Ameliorates Some Biochemical Parameters of Insulin Sensitivity in Mice

Nutrients ◽

10.3390/nu11081829 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1829 ◽

Cited By ~ 8

Author(s):

Lepore ◽

Maggisano ◽

Bulotta ◽

Mignogna ◽

Arcidiacono ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Glucose Transporter ◽

Regulatory Element ◽

Regulatory Elements ◽

High Fat

Oleacein is one of the most abundant polyphenolic compounds of olive oil, which has been shown to play a protective role against several metabolic abnormalities, including dyslipidemia, insulin resistance, and glucose intolerance. Herein, we investigated the effects of oleacein on certain markers of adipogenesis and insulin-resistance in vitro, in 3T3-L1 adipocytes, and in vivo in high-fat diet (HFD)-fed mice. During the differentiation process of 3T3-L1 preadipocytes into adipocytes, oleacein strongly inhibited lipid accumulation, and decreased protein levels of peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid synthase (FAS), while increasing Adiponectin levels. In vivo, treatment with oleacein of C57BL/6JOlaHsd mice fed with HFD for 5 and 13 weeks prevented the increase in adipocyte size and reduced the inflammatory infiltration of macrophages and lymphocytes in adipose tissue. These effects were accompanied by changes in the expression of adipose tissue-specific regulatory elements such as PPARγ, FAS, sterol regulatory element-binding transcription factor-1 (SREBP-1), and Adiponectin, while the expression of insulin-sensitive muscle/fat glucose transporter Glut-4 was restored in HFD-fed mice treated with oleacein. Collectively, our findings indicate that protection against HFD-induced adiposity by oleacein in mice is mediated by the modulation of regulators of adipogenesis. Protection against HFD-induced obesity is effective in improving peripheral insulin sensitivity.

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