Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan
IntroductionTreatment of rodents with the AT1 blocker (ARB) telmisartan (TEL) has an anti-adipose effect. Among other mechanisms, we also have attributed the anti-adipose action to diet-independent alterations in gut microbiota. Thus, we aimed here to confirm this mechanism by using the fecal microb...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-11-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1453989/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846164580927012864 |
|---|---|
| author | Marco L. Freschi Axel Künstner Gianna Huber Gianna Huber Gianna Huber Ines Stölting Hauke Busch Misa Hirose Walter Raasch Walter Raasch Walter Raasch |
| author_facet | Marco L. Freschi Axel Künstner Gianna Huber Gianna Huber Gianna Huber Ines Stölting Hauke Busch Misa Hirose Walter Raasch Walter Raasch Walter Raasch |
| author_sort | Marco L. Freschi |
| collection | DOAJ |
| description | IntroductionTreatment of rodents with the AT1 blocker (ARB) telmisartan (TEL) has an anti-adipose effect. Among other mechanisms, we also have attributed the anti-adipose action to diet-independent alterations in gut microbiota. Thus, we aimed here to confirm this mechanism by using the fecal microbiota transfer (FMT) approach.MethodsSeven weeks after initiating a high-fat diet (HFD), C57BL/6N mice received fecal microbiota for 8 weeks from donor mice by oral gavage, continuing HFD feeding. Stool samples came from mice that were treated with TEL (8 mg/kg/d by gavage, 12 weeks), thus remaining lean despite HFD feeding (BL/6>fTEL), while controls received feces samples from vehicle/HFD-treated obese mice (BL/6>fVEH). Microbiota of the stool samples from these acceptor mice was analyzed by 16S rRNA gene amplicon sequencing.ResultsWeight gain was lower in BL6>fTEL than in BL6>fVEH mice after 3 but not 8 weeks. Energy homeostasis, insulin sensitivity, and body composition did not differ between the two groups. β-diversity indicated group differences (F = 2.27, p = 0.005). Although the Firmicutes/Bacteroides ratio did not differ, abundances of distinct phyla, families, and genera varied. Among others, Ruminococcaceae and Desulfovibrionaceae, Desulfovibrionia uncl., and Lachnospiraceae uncl. were lower in BL/6>fTEL than in BL/6>fVEH mice. Moreover, the correlation between body weight and Lachnospiraceae, Desulfovibrionaceae, Desulfovibrionia uncl., or Desulfovibrio was positive in BL/6>fVEH and negative in BL/6>fTEL mice.DiscussionAs FMT from TEL-pretreated mice influences the microbiota in acceptor mice with slight weight-reducing effects, we confirm the relevance of TEL-related microbiota changes for weight reduction, most likely independent of the transferred stool-residual TEL effect on the host metabolism. |
| format | Article |
| id | doaj-art-e96eb19e48e7441fa6f4a6893a4644ac |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-e96eb19e48e7441fa6f4a6893a4644ac2024-11-18T04:23:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-11-011510.3389/fphar.2024.14539891453989Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartanMarco L. Freschi0Axel Künstner1Gianna Huber2Gianna Huber3Gianna Huber4Ines Stölting5Hauke Busch6Misa Hirose7Walter Raasch8Walter Raasch9Walter Raasch10Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, GermanyMedical Systems Biology Group, Institute of Experimental Dermatology, University of Lübeck, Lübeck, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, GermanyCBBM (Center of Brain, Behavior and Metabolism), Lübeck, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, GermanyMedical Systems Biology Group, Institute of Experimental Dermatology, University of Lübeck, Lübeck, GermanyInstitute of Experimental Dermatology, University of Lübeck, Lübeck, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, GermanyCBBM (Center of Brain, Behavior and Metabolism), Lübeck, GermanyIntroductionTreatment of rodents with the AT1 blocker (ARB) telmisartan (TEL) has an anti-adipose effect. Among other mechanisms, we also have attributed the anti-adipose action to diet-independent alterations in gut microbiota. Thus, we aimed here to confirm this mechanism by using the fecal microbiota transfer (FMT) approach.MethodsSeven weeks after initiating a high-fat diet (HFD), C57BL/6N mice received fecal microbiota for 8 weeks from donor mice by oral gavage, continuing HFD feeding. Stool samples came from mice that were treated with TEL (8 mg/kg/d by gavage, 12 weeks), thus remaining lean despite HFD feeding (BL/6>fTEL), while controls received feces samples from vehicle/HFD-treated obese mice (BL/6>fVEH). Microbiota of the stool samples from these acceptor mice was analyzed by 16S rRNA gene amplicon sequencing.ResultsWeight gain was lower in BL6>fTEL than in BL6>fVEH mice after 3 but not 8 weeks. Energy homeostasis, insulin sensitivity, and body composition did not differ between the two groups. β-diversity indicated group differences (F = 2.27, p = 0.005). Although the Firmicutes/Bacteroides ratio did not differ, abundances of distinct phyla, families, and genera varied. Among others, Ruminococcaceae and Desulfovibrionaceae, Desulfovibrionia uncl., and Lachnospiraceae uncl. were lower in BL/6>fTEL than in BL/6>fVEH mice. Moreover, the correlation between body weight and Lachnospiraceae, Desulfovibrionaceae, Desulfovibrionia uncl., or Desulfovibrio was positive in BL/6>fVEH and negative in BL/6>fTEL mice.DiscussionAs FMT from TEL-pretreated mice influences the microbiota in acceptor mice with slight weight-reducing effects, we confirm the relevance of TEL-related microbiota changes for weight reduction, most likely independent of the transferred stool-residual TEL effect on the host metabolism.https://www.frontiersin.org/articles/10.3389/fphar.2024.1453989/fullobesityrenin-angiotensin aldosterone system (RAAS)telmisartanmicrobiota transferdesulovibrioweight reduction |
| spellingShingle | Marco L. Freschi Axel Künstner Gianna Huber Gianna Huber Gianna Huber Ines Stölting Hauke Busch Misa Hirose Walter Raasch Walter Raasch Walter Raasch Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan Frontiers in Pharmacology obesity renin-angiotensin aldosterone system (RAAS) telmisartan microbiota transfer desulovibrio weight reduction |
| title | Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan |
| title_full | Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan |
| title_fullStr | Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan |
| title_full_unstemmed | Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan |
| title_short | Increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the AT1 receptor antagonist telmisartan |
| title_sort | increase in body weight is lowered when mice received fecal microbiota transfer from donor mice treated with the at1 receptor antagonist telmisartan |
| topic | obesity renin-angiotensin aldosterone system (RAAS) telmisartan microbiota transfer desulovibrio weight reduction |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1453989/full |
| work_keys_str_mv | AT marcolfreschi increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT axelkunstner increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT giannahuber increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT giannahuber increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT giannahuber increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT inesstolting increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT haukebusch increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT misahirose increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT walterraasch increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT walterraasch increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan AT walterraasch increaseinbodyweightisloweredwhenmicereceivedfecalmicrobiotatransferfromdonormicetreatedwiththeat1receptorantagonisttelmisartan |