Protein Extract of a Probiotic Strain of <i>Hafnia alvei</i> and Bacterial ClpB Protein Improve Glucose Tolerance in Mice

A commercial strain of <i>Hafnia alvei</i> (<i>H. alvei</i>) 4597 bacteria was shown to reduce food intake and promote weight loss, effects possibly induced by the bacterial protein ClpB, an antigen-mimetic of the anorexigenic α-melanocyte-stimulating hormone. A decrease in t...

Full description

Bibliographic Details
Main Authors: Vasiliy A. Zolotarev, Vladimir O. Murovets, Anastasiya L. Sepp, Egor A. Sozontov, Ekaterina A. Lukina, Raisa P. Khropycheva, Nina S. Pestereva, Irina S. Ivleva, Mouna El Mehdi, Emilie Lahaye, Nicolas Chartrel, Sergueï O. Fetissov
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/13/10590
_version_ 1797591651973070848
author Vasiliy A. Zolotarev
Vladimir O. Murovets
Anastasiya L. Sepp
Egor A. Sozontov
Ekaterina A. Lukina
Raisa P. Khropycheva
Nina S. Pestereva
Irina S. Ivleva
Mouna El Mehdi
Emilie Lahaye
Nicolas Chartrel
Sergueï O. Fetissov
author_facet Vasiliy A. Zolotarev
Vladimir O. Murovets
Anastasiya L. Sepp
Egor A. Sozontov
Ekaterina A. Lukina
Raisa P. Khropycheva
Nina S. Pestereva
Irina S. Ivleva
Mouna El Mehdi
Emilie Lahaye
Nicolas Chartrel
Sergueï O. Fetissov
author_sort Vasiliy A. Zolotarev
collection DOAJ
description A commercial strain of <i>Hafnia alvei</i> (<i>H. alvei</i>) 4597 bacteria was shown to reduce food intake and promote weight loss, effects possibly induced by the bacterial protein ClpB, an antigen-mimetic of the anorexigenic α-melanocyte-stimulating hormone. A decrease in the basal plasma glucose levels was also observed in overweight fasted humans and mice receiving <i>H. alvei</i>. However, it is not known whether <i>H. alvei</i> influences sweet taste preference and whether its protein extract or ClpB are sufficient to increase glucose tolerance; these are the objectives tested in the present study. C57BL/6J male mice were kept under standard diet and were gavaged daily for 17 days with a suspension of <i>H. alvei</i> (4.5 × 10<sup>7</sup> CFU/animal) or with <i>H. alvei</i> total protein extract (5 μg/animal) or saline as a control. Sweet taste preference was analyzed via a brief-access licking test with sucrose solution. Glucose tolerance tests (GTT) were performed after the intraperitoneal (IP) or intragastric (IG) glucose administration at the 9th and 15th days of gavage, respectively. The expression of regulatory peptides’ mRNA levels was assayed in the hypothalamus. In another experiment performed in non-treated C57BL/6J male mice, effects of acute IP administration of recombinant ClpB protein on glucose tolerance were studied by both IP- and IG-GTT. Mice treated with the <i>H. alvei</i> protein extract showed an improved glucose tolerance in IP-GTT but not in IG-GTT. Both groups treated with <i>H. alvei</i> bacteria or protein extract showed a reduction of pancreatic tissue weight but without significant changes to basal plasma insulin. No significant effects of <i>H. alvei</i> bacteria or its total protein extract administration were observed on the sweet taste preference, insulin tolerance and expression of regulatory peptides’ mRNA in the hypothalamus. Acute administration of ClpB in non-treated mice increased glucose tolerance during the IP-GTT but not the IG-GTT, and reduced basal plasma glucose levels. We conclude that both the <i>H. alvei</i> protein extract introduced orally and the ClpB protein administered via IP improve glucose tolerance probably by acting at the glucose postabsorptive level. Moreover, <i>H. alvei</i> probiotic does not seem to influence the sweet taste preference. These results justify future testing of both the <i>H. alvei</i> protein extract and ClpB protein in animal models of diabetes.
first_indexed 2024-03-11T01:40:21Z
format Article
id doaj.art-be8aeaf6f3374cfab9076338ebde2c03
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-11T01:40:21Z
publishDate 2023-06-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-be8aeaf6f3374cfab9076338ebde2c032023-11-18T16:40:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131059010.3390/ijms241310590Protein Extract of a Probiotic Strain of <i>Hafnia alvei</i> and Bacterial ClpB Protein Improve Glucose Tolerance in MiceVasiliy A. Zolotarev0Vladimir O. Murovets1Anastasiya L. Sepp2Egor A. Sozontov3Ekaterina A. Lukina4Raisa P. Khropycheva5Nina S. Pestereva6Irina S. Ivleva7Mouna El Mehdi8Emilie Lahaye9Nicolas Chartrel10Sergueï O. Fetissov11Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint-Petersburg, RussiaPavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint-Petersburg, RussiaPavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint-Petersburg, RussiaPavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint-Petersburg, RussiaPavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint-Petersburg, RussiaPavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint-Petersburg, RussiaInstitute of Experimental Medicine, 197376 Saint-Petersburg, RussiaInstitute of Experimental Medicine, 197376 Saint-Petersburg, RussiaInserm UMR1239 Laboratory, Team: Regulatory Peptides—Energy Metabolism and Motivated Behavior, University of Rouen Normandie, 76130 Mont-Saint-Aignan, FranceInserm UMR1239 Laboratory, Team: Regulatory Peptides—Energy Metabolism and Motivated Behavior, University of Rouen Normandie, 76130 Mont-Saint-Aignan, FranceInserm UMR1239 Laboratory, Team: Regulatory Peptides—Energy Metabolism and Motivated Behavior, University of Rouen Normandie, 76130 Mont-Saint-Aignan, FranceInserm UMR1239 Laboratory, Team: Regulatory Peptides—Energy Metabolism and Motivated Behavior, University of Rouen Normandie, 76130 Mont-Saint-Aignan, FranceA commercial strain of <i>Hafnia alvei</i> (<i>H. alvei</i>) 4597 bacteria was shown to reduce food intake and promote weight loss, effects possibly induced by the bacterial protein ClpB, an antigen-mimetic of the anorexigenic α-melanocyte-stimulating hormone. A decrease in the basal plasma glucose levels was also observed in overweight fasted humans and mice receiving <i>H. alvei</i>. However, it is not known whether <i>H. alvei</i> influences sweet taste preference and whether its protein extract or ClpB are sufficient to increase glucose tolerance; these are the objectives tested in the present study. C57BL/6J male mice were kept under standard diet and were gavaged daily for 17 days with a suspension of <i>H. alvei</i> (4.5 × 10<sup>7</sup> CFU/animal) or with <i>H. alvei</i> total protein extract (5 μg/animal) or saline as a control. Sweet taste preference was analyzed via a brief-access licking test with sucrose solution. Glucose tolerance tests (GTT) were performed after the intraperitoneal (IP) or intragastric (IG) glucose administration at the 9th and 15th days of gavage, respectively. The expression of regulatory peptides’ mRNA levels was assayed in the hypothalamus. In another experiment performed in non-treated C57BL/6J male mice, effects of acute IP administration of recombinant ClpB protein on glucose tolerance were studied by both IP- and IG-GTT. Mice treated with the <i>H. alvei</i> protein extract showed an improved glucose tolerance in IP-GTT but not in IG-GTT. Both groups treated with <i>H. alvei</i> bacteria or protein extract showed a reduction of pancreatic tissue weight but without significant changes to basal plasma insulin. No significant effects of <i>H. alvei</i> bacteria or its total protein extract administration were observed on the sweet taste preference, insulin tolerance and expression of regulatory peptides’ mRNA in the hypothalamus. Acute administration of ClpB in non-treated mice increased glucose tolerance during the IP-GTT but not the IG-GTT, and reduced basal plasma glucose levels. We conclude that both the <i>H. alvei</i> protein extract introduced orally and the ClpB protein administered via IP improve glucose tolerance probably by acting at the glucose postabsorptive level. Moreover, <i>H. alvei</i> probiotic does not seem to influence the sweet taste preference. These results justify future testing of both the <i>H. alvei</i> protein extract and ClpB protein in animal models of diabetes.https://www.mdpi.com/1422-0067/24/13/10590glucose metabolismglucose toleranceinsulinsweet tasteprobiotics<i>Hafnia alvei</i>
spellingShingle Vasiliy A. Zolotarev
Vladimir O. Murovets
Anastasiya L. Sepp
Egor A. Sozontov
Ekaterina A. Lukina
Raisa P. Khropycheva
Nina S. Pestereva
Irina S. Ivleva
Mouna El Mehdi
Emilie Lahaye
Nicolas Chartrel
Sergueï O. Fetissov
Protein Extract of a Probiotic Strain of <i>Hafnia alvei</i> and Bacterial ClpB Protein Improve Glucose Tolerance in Mice
International Journal of Molecular Sciences
glucose metabolism
glucose tolerance
insulin
sweet taste
probiotics
<i>Hafnia alvei</i>
title Protein Extract of a Probiotic Strain of <i>Hafnia alvei</i> and Bacterial ClpB Protein Improve Glucose Tolerance in Mice
title_full Protein Extract of a Probiotic Strain of <i>Hafnia alvei</i> and Bacterial ClpB Protein Improve Glucose Tolerance in Mice
title_fullStr Protein Extract of a Probiotic Strain of <i>Hafnia alvei</i> and Bacterial ClpB Protein Improve Glucose Tolerance in Mice
title_full_unstemmed Protein Extract of a Probiotic Strain of <i>Hafnia alvei</i> and Bacterial ClpB Protein Improve Glucose Tolerance in Mice
title_short Protein Extract of a Probiotic Strain of <i>Hafnia alvei</i> and Bacterial ClpB Protein Improve Glucose Tolerance in Mice
title_sort protein extract of a probiotic strain of i hafnia alvei i and bacterial clpb protein improve glucose tolerance in mice
topic glucose metabolism
glucose tolerance
insulin
sweet taste
probiotics
<i>Hafnia alvei</i>
url https://www.mdpi.com/1422-0067/24/13/10590
work_keys_str_mv AT vasiliyazolotarev proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT vladimiromurovets proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT anastasiyalsepp proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT egorasozontov proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT ekaterinaalukina proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT raisapkhropycheva proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT ninaspestereva proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT irinasivleva proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT mounaelmehdi proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT emilielahaye proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT nicolaschartrel proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice
AT sergueiofetissov proteinextractofaprobioticstrainofihafniaalveiiandbacterialclpbproteinimproveglucosetoleranceinmice