Xylo-Oligosaccharides in Prevention of Hepatic Steatosis and Adipose Tissue Inflammation: Associating Taxonomic and Metabolomic Patterns in Fecal Microbiomes with Biclustering

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms associated with these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12 weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

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Xylo-Oligosaccharides in Prevention of Hepatic Steatosis and Adipose Tissue Inflammation: Associating Taxonomic and Metabolomic Patterns in Fecal Microbiomes with Biclustering

10.20944/preprints202103.0001.v1 ◽

2021 ◽

Author(s):

Jukka Hintikka ◽

Sanna Lensu ◽

Elina Mäkinen ◽

Sira Karvinen ◽

Marjaana Honkanen ◽

...

Keyword(s):

Amino Acids ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

Insulin Signaling ◽

Aromatic Amino Acids ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Beneficial Effects ◽

Male Wistar Rats ◽

Branched Chain

We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms behind these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12-weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.

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A Novel Combination of Fruits and Vegetables Prevents Diet-Induced Hepatic Steatosis and Metabolic Dysfunction in Mice

Journal of Nutrition ◽

10.1093/jn/nxaa259 ◽

2020 ◽

Vol 150 (11) ◽

pp. 2950-2960

Author(s):

Weimin Guo ◽

Dayong Wu ◽

Maria C Dao ◽

Lijun Li ◽

Erin D Lewis ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

Gut Microbiota ◽

Hepatic Steatosis ◽

Fruits And Vegetables ◽

Causal Relation ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Freeze Dried ◽

Underlying Mechanisms

ABSTRACT Background Epidemiological studies suggest that higher fruits and vegetables (F&V) consumption correlates with reduced risk of hepatic steatosis, yet evidence for causality and the underlying mechanisms is lacking. Objectives We aimed to determine the causal relation between F&V consumption and improved metabolic disorders in mice fed high-fat (HF) (Experiment-1) or normal-fat (Experiment-2) diets and its underlying mechanisms. Methods Six-week-old male C57BL/6J mice were randomly grouped and fed diets supplemented at 0%–15% (wt:wt) with a freeze-dried powder composed of 24 commonly consumed F&V (human equivalent of 0–9 servings/d) for 20 wk. In Experiment-1, mice were fed an HF (45% kcal fat) diet with 0% (HF0), 5%, 10%, or 15% (HF15) F&V or a matched low-fat control diet (10% kcal fat). In Experiment-2, mice were fed an AIN-93 diet (basal) (B, 16% kcal fat) with 0% (B0), 5%, 10%, or 15% (B15) F&V supplementation. Body weight and composition, food intake, hepatic steatosis, inflammation, ceramide levels, sphingomyelinase activity, and gut microbiota were assessed. Results In Experiment-1, mice fed the HF15 diet had lower weight gain (17.9%), hepatic steatosis (48.4%), adipose tissue inflammation, blood (24.6%) and liver (33.9%) ceramide concentrations, and sphingomyelinase activity (38.8%) than HF0 mice (P < 0.05 for all). In Experiment-2, mice fed the B15 diet had no significant changes in weight gain but showed less hepatic steatosis (28.5%), blood and adipose tissue inflammation, and lower blood (30.0%) ceramide concentrations than B0 mice (P < 0.05 for all). These F&V effects were associated with favorable microbiota changes. Conclusions These findings represent the first evidence for a causal role of high F&V intake in mitigating hepatic steatosis in mice. These beneficial effects may be mediated through changes in ceramide and/or gut microbiota, and suggest that higher than currently recommended servings of F&V may be needed to achieve maximum health benefits.

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Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice

Nutrients ◽

10.3390/nu12020342 ◽

2020 ◽

Vol 12 (2) ◽

pp. 342 ◽

Cited By ~ 2

Author(s):

Alexandra Marziou ◽

Clothilde Philouze ◽

Charlène Couturier ◽

Julien Astier ◽

Philippe Obert ◽

...

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

De Novo ◽

De Novo Lipogenesis ◽

Acid Oxidation ◽

Mrna Levels ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Triglyceride Accumulation

The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect of VD supplementation on obesity and associated disorders was evaluated in high-fat- and high-sucrose (HFS)-fed mice. Morphological, histological, and molecular phenotype were characterized. The increased body mass and adiposity caused by HFS diet as well as fat cell hypertrophy and glucose homeostasis were not improved by VD supplementation. However, VD supplementation led to a decrease of HFS-induced inflammation in inguinal adipose tissue, characterized by a decreased expression of chemokine mRNA levels. Moreover, a protective effect of VD on HFS-induced hepatic steatosis was highlighted by a decrease of lipid droplets and a reduction of triglyceride accumulation in the liver. This result was associated with a significant decrease of gene expression coding for key enzymes involved in hepatic de novo lipogenesis and fatty acid oxidation. Altogether, our results show that VD supplementation could be of interest to blunt the adipose tissue inflammation and hepatic steatosis and could represent an interesting nutritional strategy to fight obesity-associated comorbidities.

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Vitamin D Receptor Modulates Intestinal Lipid Metabolism, Adipose Tissue Inflammation and Hepatic Steatosis in Diet-induced Obese Mice

Zeitschrift für Gastroenterologie ◽

10.1055/s-0035-1568058 ◽

2015 ◽

Vol 53 (12) ◽

Author(s):

D Jahn ◽

JC Fleet ◽

D Kraus ◽

J Schmitt ◽

HM Hermanns ◽

...

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Lipid Metabolism ◽

Hepatic Steatosis ◽

Vitamin D Receptor ◽

Adipose Tissue Inflammation ◽

Obese Mice ◽

Tissue Inflammation

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Tissue Inhibitor of Metalloproteinase 3 Deficiency Causes Hepatic Steatosis and Adipose Tissue Inflammation in Mice

Gastroenterology ◽

10.1053/j.gastro.2008.10.079 ◽

2009 ◽

Vol 136 (2) ◽

pp. 663-672.e4 ◽

Cited By ~ 76

Author(s):

Rossella Menghini ◽

Stefano Menini ◽

Roberta Amoruso ◽

Loredana Fiorentino ◽

Viviana Casagrande ◽

...

Keyword(s):

Adipose Tissue ◽

Hepatic Steatosis ◽

Tissue Inhibitor Of Metalloproteinase ◽

Adipose Tissue Inflammation ◽

Tissue Inhibitor ◽

Tissue Inflammation

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Role of RAGE in obesity-induced adipose tissue inflammation and insulin resistance

Cell Death Discovery ◽

10.1038/s41420-021-00711-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Ziqian Feng ◽

Zuoqin Du ◽

Xin Shu ◽

Luochen Zhu ◽

Jiaqi Wu ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Signaling ◽

Macrophage Polarization ◽

Chow Diet ◽

Cell Trafficking ◽

Adipose Tissue Inflammation ◽

Blood Monocytes ◽

Adipose Tissues ◽

Tissue Inflammation

AbatractObesity is known to be associated with adipose tissue inflammation and insulin resistance. Importantly, in obesity, the accumulation of proinflammatory macrophages in adipose tissue correlates with insulin resistance. We hypothesized that the receptor for advanced glycation end products (RAGE) and associated ligands are involved in adipose tissue insulin resistance, and that the activation of the AGE–RAGE axis plays an important role in obesity-associated inflammation. C57BL/6J mice (WT) and RAGE deficient (RAGE−/−) mice were fed a high fat diet (HFD) and subjected to glucose and insulin tolerance tests. Epdidymal adipose tissue (eAT) was collected and adipose stromal vascular cells isolated using flow cytometry. Visceral adipose tissue macrophage polarization was assessed by quantitative real time PCR. Immunoblotting was performed to evaluate the insulin signaling in adipose tissues. In additional studies, cell trafficking was assessed by injecting labeled blood monocytes into recipient mice. RAGE−/− mice displayed improved insulin sensitivity and glucose tolerance, accompanied by decreased body weight and eAT mass. Exogenous methylglyoxal (MGO) impaired insulin-stimulated AKT signaling in adipose tissues from WT mice fed a normal chow diet, but not in RAGE−/− mice. In contrast, in obese mice, treatment with MGO did not reduce insulin-induced phosphorylation of AKT in WT-HFD mice. Moreover, insulin-induced AKT phosphorylation was found to be impaired in adipose tissue from RAGE−/−-HFD mice. RAGE−/− mice displayed improved inflammatory profiles and evidence for increased adipose tissue browning. This observation is consistent with the finding of reduced plasma levels of FFA, glycerol, IL-6, and leptin in RAGE−/− mice compared to WT mice. Collectively the data demonstrate that RAGE-mediated adipose tissue inflammation and insulin-signaling are potentially important mechanisms that contribute to the development of obesity-associated insulin resistance.

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Dietary sphingomyelin attenuates hepatic steatosis and adipose tissue inflammation in high-fat-diet-induced obese mice

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2016.09.017 ◽

2017 ◽

Vol 40 ◽

pp. 36-43 ◽

Cited By ~ 51

Author(s):

Gregory H. Norris ◽

Caitlin M. Porter ◽

Christina Jiang ◽

Courtney L. Millar ◽

Christopher N. Blesso

Keyword(s):

Adipose Tissue ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Adipose Tissue Inflammation ◽

Obese Mice ◽

High Fat ◽

Tissue Inflammation

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Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00054.2009 ◽

2009 ◽

Vol 296 (5) ◽

pp. E1164-E1171 ◽

Cited By ~ 121

Author(s):

Victoria J. Vieira ◽

Rudy J. Valentine ◽

Kenneth R. Wilund ◽

Nirav Antao ◽

Tracy Baynard ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

Adipose Tissue Inflammation ◽

Obese Mice ◽

Metabolic Disturbances ◽

Low Fat ◽

Tissue Inflammation ◽

Low Fat Diet ◽

Tnf Α

Adipose tissue inflammation causes metabolic disturbances, including insulin resistance and hepatic steatosis. Exercise training (EX) may decrease adipose tissue inflammation, thereby ameliorating such disturbances, even in the absence of fat loss. The purpose of this study was to 1) compare the effects of low-fat diet (LFD), EX, and their combination on inflammation, insulin resistance, and hepatic steatosis in high-fat diet-induced obese mice and 2) determine the effect of intervention duration (i.e., 6 vs. 12 wk). C57BL/6 mice ( n = 109) fed a 45% fat diet (HFD) for 6 wk were randomly assigned to an EX (treadmill: 5 days/wk, 6 or 12 wk, 40 min/day, 65–70% V̇o2max) or sedentary (SED) group. Mice remained on HFD or were placed on a 10% fat diet (LFD) for 6 or 12 wk. Following interventions, fat pads were weighed and expressed relative to body weight; hepatic steatosis was assessed by total liver triglyceride and insulin resistance by HOMA-IR and glucose AUC. RT-PCR was used to determine adipose gene expression of MCP-1, F4/80, TNF-α, and leptin. By 12 wk, MCP-1, F4/80, and TNF-α mRNA were reduced by EX and LFD. Exercise ( P = 0.02), adiposity ( P = 0.03), and adipose F4/80 ( P = 0.02) predicted reductions in HOMA-IR ( r2 = 0.75, P < 0.001); only adiposity ( P = 0.04) predicted improvements in hepatic steatosis ( r2 = 0.51, P < 0.001). Compared with LFD, EX attenuated increases in adiposity, hepatic steatosis, and adipose MCP-1 expression from 6 to 12 wk. There are unique metabolic consequences of a sedentary lifestyle and HFD that are most evident long term, highlighting the importance of both EX and LFD in preventing obesity-related metabolic disturbances.

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