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Article ; Online: Metformin treatment for 8 days impacts multiple intestinal parameters in high-fat high-sucrose fed mice

Amélie Bravard / Céline Gérard / Clémence Defois / Bérengère Benoit / Kassem Makki / Emmanuelle Meugnier / Dominique Rainteau / Jennifer Rieusset / Murielle Godet / Hubert Vidal

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 12

Abstract: Abstract Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the ... ...

Abstract	Abstract Although the mechanism of action of the antidiabetic drug metformin is still a matter of discussions, it is well accepted that the gut plays an important role. To gain more insights into the mechanisms occurring in the different regions of the intestine, adult male mice were fed a high-fat-high sucrose (HFS) diet for 8 days and treated with metformin by gavage (300 mg/day/kg body weight) during the HFS diet. Metformin counteracted HFS diet-induced overexpression of a network of genes involved in the transport of glucose and fatty acids in the different regions of the small intestine. It also induced beneficial modification of secondary bile acid profile in the caecum, with a reduction of deoxycholic acid and lithocholic acid levels and increased abundance of ursodeoxycholic acid and tauroursodeoxycholic acid, potentially leading to FRX inhibition. In parallel, metformin treatment was associated with specific changes of the microbiota composition in the lumen of the different regions of the intestine. Metformin induced a marked increase in the abundance of Akkermansia muciniphila in the lumen all along the gut and counteracted the effects of HFS diet on the abundances of some bacterial groups generally associated with metabolic disturbances (f-Lachnospiraceae, f-Petostreptococcaceae, g-Clostidium). Therefore, the present work clearly emphasises the role of all the regions of the intestinal tract in the beneficial action of the antidiabetic drug metformin in a prediabetic mouse model.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Blood-derived miRNA levels are not correlated with metabolic or anthropometric parameters in obese pre-diabetic subjects but with systemic inflammation.

Prabu Paramasivam / Emmanuelle Meugnier / Kuppan Gokulakrishnan / Harish Ranjini / Lisa R Staimez / Mary Beth Weber / K M Venkat Narayan / Hubert Vidal / Nikhil Tandon / Dorairaj Prabhakaran / Anjana Ranjit Mohan / Viswanathan Mohan / Sophie Rome / Muthuswamy Balasubramanyam

PLoS ONE, Vol 17, Iss 2, p e

2022 Volume 0263479

Abstract: As blood-derived miRNAs (c-miRNAs) are modulated by exercise and nutrition, we postulated that they might be used to monitor the effects of a lifestyle intervention (LI) to prevent diabetes development. To challenge this hypothesis, obese Asian Indian ... ...

Abstract	As blood-derived miRNAs (c-miRNAs) are modulated by exercise and nutrition, we postulated that they might be used to monitor the effects of a lifestyle intervention (LI) to prevent diabetes development. To challenge this hypothesis, obese Asian Indian pre-diabetic patients were submitted to diet modifications and physical activity for 4 months (LI group) and compared to a control group which was given recommendations only. We have considered 2 periods of time to analyze the data, i.e.; a first one to study the response to the intervention (4 months), and a second one post-intervention (8 months). At basal, 4 months and 8 months post-intervention the levels of 17 c-miRNAs were quantified, selected either for their relevance to the pathology or because they are known to be modulated by physical activity or diet. Their variations were correlated with variations of 25 metabolic and anthropometric parameters and cytokines. As expected, fasting-glycaemia, insulin-sensitivity, levels of exercise- and obesity-induced cytokines were ameliorated after 4 months. In addition, the levels of 4 miRNAs (i.e.; miR-128-3p, miR-374a-5p, miR-221-3p, and miR-133a-3p) were changed only in the LI group and were correlated with metabolic improvement (insulin sensitivity, cytokine levels, waist circumference and systolic blood pressure). However, 8 months post-intervention almost all ameliorated metabolic parameters declined indicating that the volunteers did not continue the protocol on their own. Surprisingly, the LI positive effects on c-miRNA levels were still detected, and were even more pronounced 8 months post-intervention. In parallel, MCP-1, involved in tissue infiltration by immune cells, and Il-6, adiponectin and irisin, which have anti-inflammatory effects, continued to be significantly and positively modified, 8 months post-intervention. These data demonstrated for the first time, that c-miRNA correlations with metabolic parameters and insulin sensitivity are in fact only indirect and likely associated with the level ...
Keywords	Medicine ; R ; Science ; Q
Subject code	796
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Profiling of ob/ob mice skeletal muscle exosome-like vesicles demonstrates combined action of miRNAs, proteins and lipids to modulate lipid homeostasis in recipient cells

Audrey Jalabert / Laura Reininger / Emmanuelle Berger / Yohann Coute / Emmanuelle Meugnier / Alexis Forterre / Elizabeth Errazuriz-Cerda / Alain Geloen / Myriam Aouadi / Karim Bouzakri / Jennifer Rieusset / Sophie Rome

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 17

Abstract: Abstract We have determined the lipid, protein and miRNA composition of skeletal muscle (SkM)-released extracellular vesicles (ELVs) from Ob/ob (OB) vs wild-type (WT) mice. The results showed that atrophic insulin-resistant OB-SkM released less ELVs than ...

Abstract	Abstract We have determined the lipid, protein and miRNA composition of skeletal muscle (SkM)-released extracellular vesicles (ELVs) from Ob/ob (OB) vs wild-type (WT) mice. The results showed that atrophic insulin-resistant OB-SkM released less ELVs than WT-SkM, highlighted by a RAB35 decrease and an increase in intramuscular cholesterol content. Proteomic analyses of OB-ELVs revealed a group of 37 proteins functionally connected, involved in lipid oxidation and with catalytic activities. OB-ELVs had modified contents for phosphatidylcholine (PC 34-4, PC 40-3 and PC 34-0), sphingomyelin (Sm d18:1/18:1) and ceramides (Cer d18:1/18:0) and were enriched in cholesterol, likely to alleviated intracellular accumulation. Surprisingly many ELV miRNAs had a nuclear addressing sequence, and targeted genes encoding proteins with nuclear activities. Interestingly, SkM-ELV miRNA did not target mitochondria. The most significant function targeted by the 7 miRNAs altered in OB-ELVs was lipid metabolism. In agreement, OB-ELVs induced lipid storage in recipient adipocytes and increased lipid up-take and fatty acid oxidation in recipient muscle cells. In addition, OB-ELVs altered insulin-sensitivity and induced atrophy in muscle cells, reproducing the phenotype of the releasing OB muscles. These data suggest for the first time, a cross-talk between muscle cells and adipocytes, through the SkM-ELV route, in favor of adipose tissue expansion.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vitamin D status modulates mitochondrial oxidative capacities in skeletal muscle

Communications Biology, Vol 5, Iss 1, Pp 1-

role in sarcopenia

2022 Volume 15

Abstract: Vitamin D has an impact on mitochondrial biogenesis and oxidative activity in skeletal muscle both in vitro and in vivo, and vitamin D supplementation in older people may improve muscle mass and strength. ...

Abstract	Vitamin D has an impact on mitochondrial biogenesis and oxidative activity in skeletal muscle both in vitro and in vivo, and vitamin D supplementation in older people may improve muscle mass and strength.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear

Cells, Vol 10, Iss 1873, p

2021 Volume 1873

Abstract: Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study ... ...

Abstract	Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Using RNA sequencing, we identified 4415 differentially expressed genes, including 1746 up- and 2369 down-regulated genes, in bear muscles between the active versus hibernating period. We focused on the Transforming Growth Factor (TGF)-β and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-β- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. This was further substantiated at the protein level. Our data suggest TGF-β/BMP balance is crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-β inhibiting therapies already targeted to prevent muscle atrophy.
Keywords	brown bear hibernation ; mouse unloading ; muscle atrophy ; physical inactivity ; RNA sequencing ; TGF-β/BMP signaling ; Biology (General) ; QH301-705.5
Subject code	630
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Low-dose pollutant mixture triggers metabolic disturbances in female mice leading to common and specific features as compared to a high-fat diet

Labaronne, Emmanuel / Benoit Julien / Brigitte Le Magueresse-Battistoni / Claudie Pinteur / Danielle Naville / Emmanuelle Meugnier-Fouilloux / Hubert Vidal / Nathalie Vega / Sandra Pesenti

Journal of nutritional biochemistry. 2017 July, v. 45

2017

Abstract: Environmental pollutants are potential etiologic factors of obesity and diabetes that reach epidemic proportions worldwide. However, it is important to determine if pollutants could exert metabolic defects without directly inducing obesity. The metabolic ...

Abstract	Environmental pollutants are potential etiologic factors of obesity and diabetes that reach epidemic proportions worldwide. However, it is important to determine if pollutants could exert metabolic defects without directly inducing obesity. The metabolic disturbances triggered in nonobese mice lifelong exposed to a mixture of low-dose pollutants (2,3,7,8-tetrachlorodibenzo-p-dioxine, polychlorinated biphenyl 153, diethylhexyl-phthalate, and bisphenol A) were compared with changes provoked by a high-fat high-sucrose (HFHS) diet not containing the pollutant mixture. Interestingly, females exposed to pollutants exhibited modifications in lipid homeostasis including a significant increase of hepatic triglycerides but also distinct features from those observed in diet-induced obese mice. For example, they did not gain weight nor was glucose tolerance impacted. To get more insight, a transcriptomic analysis was performed in liver for comparison. We observed that in addition to the xenobiotic/drug metabolism pathway, analysis of the hepatic signature illustrated that the steroid/cholesterol, fatty acid/lipid and circadian clock metabolic pathways were targeted in response to pollutants as observed in the diet-induced obese mice. However, the specific sets of dysregulated annotated genes (>1300) did not overlap more than 40% between both challenges with some genes specifically altered only in response to pollutant exposure. Collectively, results show that pollutants and HFHS affect common metabolic pathways, but by different, albeit overlapping, mechanisms. This is highly relevant for understanding the synergistic effects between pollutants and the obesogenic diet reported in the literature.
Keywords	animal disease models ; biochemical pathways ; bisphenol A ; cholesterol ; circadian rhythm ; diabetes ; etiology ; fatty acids ; females ; genes ; glucose tolerance ; high fat diet ; homeostasis ; liver ; mice ; obesity ; obesogenic diet ; pharmacokinetics ; pollutants ; polychlorinated biphenyls ; synergism ; transcriptomics ; triacylglycerols ; xenobiotics
Language	English
Dates of publication	2017-07
Size	p. 83-93.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2017.04.001
Database	NAL-Catalogue (AGRICOLA)

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Article: Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets

Lecomte, Manon / Alain Géloën / Annie Durand / Carole Vaysse / Emmanuelle Loizon / Emmanuelle Meugnier / Fabienne Laugerette / Florent Joffre / Leslie Couëdelo / Marie-Caroline Michalski / Pascale Plaisancié

Journal of nutritional biochemistry. 2017 May, v. 43

2017

Abstract: Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in ... ...

Abstract	Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods.
Keywords	adipose tissue ; alpha-linolenic acid ; artificial diets ; dietary fat ; emulsifiers ; endotoxemia ; endotoxins ; fatty acid composition ; foods ; high fat diet ; inflammation ; linseed ; linseed oil ; lipid metabolism ; mice ; noninsulin-dependent diabetes mellitus ; obesity ; palm oils ; receptors ; soybeans ; transporters
Language	English
Dates of publication	2017-05
Size	p. 116-124.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1014929-6
ISSN	1873-4847 ; 0955-2863
ISSN (online)	1873-4847
ISSN	0955-2863
DOI	10.1016/j.jnutbio.2017.02.004
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Low level activity thresholds for changes in NMR biomarkers and genes in high risk subjects for Type 2 Diabetes

Karl-Heinz Herzig / Juhani Leppäluoto / Jari Jokelainen / Emmanuelle Meugnier / Sandra Pesenti / Harri Selänne / Kari A. Mäkelä / Riikka Ahola / Timo Jämsä / Hubert Vidal / Sirkka Keinänen-Kiukaanniemi

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 10

Abstract: Abstract Our objectives were to determine if there are quantitative associations between amounts and intensities of physical activities (PA) on NMR biomarkers and changes in skeletal muscle gene expressions in subjects with high risk for type 2 diabetes ( ...

Abstract	Abstract Our objectives were to determine if there are quantitative associations between amounts and intensities of physical activities (PA) on NMR biomarkers and changes in skeletal muscle gene expressions in subjects with high risk for type 2 diabetes (T2D) performing a 3-month PA intervention. We found that PA was associated with beneficial biomarker changes in a factor containing several VLDL and HDL subclasses and lipids in principal component analysis (P = <0.01). Division of PA into quartiles demonstrated significant changes in NMR biomarkers in the 2nd - 4th quartiles compared to the 1st quartile representing PA of less than 2850 daily steps (P = 0.0036). Mediation analysis of PA-related reductions in lipoproteins showed that the effects of PA was 4–15 times greater than those of body weight or fat mass reductions. In a subset study in highly active subjects’ gene expressions of oxidative fiber markers, Apo D, and G0/G1 Switch Gene 2, controlling insulin signaling and glucose metabolism were significantly increased. Slow walking at speeds of 2–3 km/h exceeding 2895 steps/day attenuated several circulating lipoprotein lipids. The effects were mediated rather by PA than body weight or fat loss. Thus, lower thresholds for PA may exist for long term prevention of cardio-metabolic diseases in sedentary overweight subjects.
Keywords	Medicine ; R ; Science ; Q
Subject code	796
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Fructose overfeeding in firstâdegree relatives of type 2 diabetic patients impacts energy metabolism and mitochondrial functions in skeletal muscle

Seyssel, Kevin / Christine Durand / Emilie Blond / Emmanuel Disse / Emmanuelle Meugnier / Hubert Vidal / John Brozek / KimâAnne LÃª / Laurent Pays / Luc Tappy / Martine Laville / Serge Nataf

Molecular nutrition & food research. 2016 Dec., v. 60, no. 12

2016

Abstract: SCOPE: The aim of the study was to assess the effects of a highâfructose diet (HFrD) on skeletal muscle transcriptomic response in healthy offspring of patients with type 2 diabetes, a subgroup of individuals prone to metabolic disorders. METHODS AND ... ...

Abstract	SCOPE: The aim of the study was to assess the effects of a highâfructose diet (HFrD) on skeletal muscle transcriptomic response in healthy offspring of patients with type 2 diabetes, a subgroup of individuals prone to metabolic disorders. METHODS AND RESULTS: Ten healthy normal weight firstâdegree relatives of type 2 diabetic patients were submitted to a HFrD (+3.5 g fructose/kg fatâfree mass per day) during 7 days. A global transcriptomic analysis was performed on skeletal muscle biopsies combined with in vitro experiments using primary myotubes. Transcriptomic analysis highlighted profound effects on fatty acid oxidation and mitochondrial pathways supporting the wholeâbody metabolic shift with the preferential use of carbohydrates instead of lipids. Bioinformatics tools pointed out possible transcription factors orchestrating this genomic regulation, such as PPARÎ± and NR4A2. In vitro experiments in human myotubes suggested an indirect action of fructose in skeletal muscle, which seemed to be independent from lactate, uric acid, or nitric oxide. CONCLUSION: This study shows therefore that a large cluster of genes related to energy metabolism, mitochondrial function, and lipid oxidation was downregulated after 7 days of HFrD, thus supporting the concept that overconsumption of fructoseâcontaining foods could contribute to metabolic deterioration in humans.
Keywords	beta oxidation ; bioinformatics ; biopsy ; diet ; energy metabolism ; foods ; fructose ; gene expression regulation ; genes ; genomics ; humans ; in vitro studies ; lactic acid ; lean body mass ; lipid peroxidation ; lipids ; mitochondria ; myotubes ; nitric oxide ; noninsulin-dependent diabetes mellitus ; overfeeding ; patients ; progeny ; skeletal muscle ; transcription (genetics) ; transcription factors ; transcriptomics ; uric acid
Language	English
Dates of publication	2016-12
Size	p. 2691-2699.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2160372-8
ISSN	1613-4133 ; 1613-4125
ISSN (online)	1613-4133
ISSN	1613-4125
DOI	10.1002/mnfr.201600407
Database	NAL-Catalogue (AGRICOLA)

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Article: Oral administration of a casein matrix containing β-casofensin protects the intestinal barrier in two preclinical models of gut diseases

Bessette, Claudine / Bérengère Benoit / Emmanuelle Meugnier / Gwénaële Henry / Jérémie Bruno / Joelle Léonil / Laurent Ferrier / Pascale Plaisancié / Soraya Sekkal / Vassilia Théodorou

Journal of functional foods. 2016 Dec., v. 27

2016

Abstract: β-Casofensin is a milk-derived bioactive peptide that interacts with intestinal goblet cells. We aimed to determine whether β-casofensin could prevent intestinal dysfunctions induced by neonatal maternal separation (NMS) and whether it retains its ... ...

Abstract	β-Casofensin is a milk-derived bioactive peptide that interacts with intestinal goblet cells. We aimed to determine whether β-casofensin could prevent intestinal dysfunctions induced by neonatal maternal separation (NMS) and whether it retains its protective effects when administered in a casein matrix. We also evaluated whether a casein matrix enriched in β-casofensin protects against intestinal enteritis induced by indomethacin. β-Casofensin abolished NMS-induced jejunal hyperpermeability and prevented the depletion of goblet and Paneth cells induced by NMS. In addition, β-casofensin maintained its effectiveness against NMS-induced intestinal barrier alterations when administered in a casein matrix. A casein matrix containing β-casofensin also reduced intestinal damages induced by indomethacin. A functional food containing β-casofensin may prevent both the deleterious effects of neonatal stress on the intestinal barrier and indomethacin-induced enteritis. These results suggest a promising application of β-casofensin as a gut barrier protector in the context of bioactive foods and clinical nutrition.
Keywords	absorption barrier ; casein ; clinical nutrition ; enteritis ; functional foods ; goblet cells ; indomethacin ; jejunum ; models ; oral administration ; protective effect
Language	English
Dates of publication	2016-12
Size	p. 223-235.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2511964-3
ISSN	1756-4646
ISSN	1756-4646
DOI	10.1016/j.jff.2016.09.007
Database	NAL-Catalogue (AGRICOLA)

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