Long-term metabolic effects of malnutrition: Liver steatosis and insulin resistance following early-life protein restriction
Early postnatal-life malnutrition remains prevalent globally, and about 45% of all child deaths are linked to malnutrition. It is not clear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when they are later in life exposed to a fat and carbohydrate ri...
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| creator | Dalvi, Prasad S Yang, Steven Swain, Nathan Kim, Junsoo Saha, Senjuti Bourdon, Celine Zhang, Ling Chami, Rose Bandsma, Robert H J |
| description | Early postnatal-life malnutrition remains prevalent globally, and about 45% of all child deaths are linked to malnutrition. It is not clear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when they are later in life exposed to a fat and carbohydrate rich obesogenic diet. The lack of knowledge around this dietary "double burden" warrants studies to understand the long-term consequences of children previously exposed to malnutrition. We hypothesized that an early-life nutritional insult of low protein consumption in mice would lead to long-term metabolic disturbances that would exacerbate the development of diet-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD). We investigated the effects of feeding a low protein diet (4% wt/wt) immediately after weaning for four weeks and subsequent feeding of a high carbohydrate high fat feeding for 16 weeks on metabolic function and development of NAFLD. Mice exposed to early-life protein restriction demonstrated a transient glucose intolerance upon recovery by regular chow diet feeding. However, protein restriction after weaning in mice did not exacerbate an obesogenic diet-induced insulin resistance or progression to NAFLD. These data suggest that transient protein restriction in early-life does not exacerbate an obesogenic diet-induced NAFLD and insulin resistance. |
| doi_str_mv | 10.1371/journal.pone.0199916 |
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It is not clear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when they are later in life exposed to a fat and carbohydrate rich obesogenic diet. The lack of knowledge around this dietary "double burden" warrants studies to understand the long-term consequences of children previously exposed to malnutrition. We hypothesized that an early-life nutritional insult of low protein consumption in mice would lead to long-term metabolic disturbances that would exacerbate the development of diet-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD). We investigated the effects of feeding a low protein diet (4% wt/wt) immediately after weaning for four weeks and subsequent feeding of a high carbohydrate high fat feeding for 16 weeks on metabolic function and development of NAFLD. Mice exposed to early-life protein restriction demonstrated a transient glucose intolerance upon recovery by regular chow diet feeding. However, protein restriction after weaning in mice did not exacerbate an obesogenic diet-induced insulin resistance or progression to NAFLD. These data suggest that transient protein restriction in early-life does not exacerbate an obesogenic diet-induced NAFLD and insulin resistance.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0199916</identifier><identifier>PMID: 29965973</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology and Life Sciences ; Carbohydrates ; Child malnutrition ; Children ; Chronic illnesses ; Complications and side effects ; Developing countries ; Diabetes ; Diet ; Diet, Protein-Restricted - adverse effects ; Endocrinology ; Exposure ; Famine ; Fatty change ; Fatty liver ; Feeding ; Female ; Gene expression ; Glucose - metabolism ; Glucose Intolerance - etiology ; Glucose Intolerance - metabolism ; Glucose Intolerance - pathology ; Glucose tolerance ; Homeostasis ; Hospitals ; Inflammation ; Insulin ; Insulin Resistance ; Intolerance ; Laboratories ; LDCs ; Liver ; Liver diseases ; Low protein diet ; Male ; Malnutrition ; Medicine ; Medicine and Health Sciences ; Metabolic diseases ; Metabolic disorders ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease - etiology ; Non-alcoholic Fatty Liver Disease - metabolism ; Non-alcoholic Fatty Liver Disease - pathology ; Nutrient deficiency ; Nutrition research ; Obesity ; Protein deficiency ; Protein-Energy Malnutrition - complications ; Protein-Energy Malnutrition - physiopathology ; Proteins ; Research and Analysis Methods ; Risk factors ; Rodents ; Steatosis ; Weaning</subject><ispartof>PloS one, 2018-07, Vol.13 (7), p.e0199916-e0199916</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Dalvi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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It is not clear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when they are later in life exposed to a fat and carbohydrate rich obesogenic diet. The lack of knowledge around this dietary "double burden" warrants studies to understand the long-term consequences of children previously exposed to malnutrition. We hypothesized that an early-life nutritional insult of low protein consumption in mice would lead to long-term metabolic disturbances that would exacerbate the development of diet-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD). We investigated the effects of feeding a low protein diet (4% wt/wt) immediately after weaning for four weeks and subsequent feeding of a high carbohydrate high fat feeding for 16 weeks on metabolic function and development of NAFLD. Mice exposed to early-life protein restriction demonstrated a transient glucose intolerance upon recovery by regular chow diet feeding. 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etiology</subject><subject>Non-alcoholic Fatty Liver Disease - metabolism</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Nutrient deficiency</subject><subject>Nutrition research</subject><subject>Obesity</subject><subject>Protein deficiency</subject><subject>Protein-Energy Malnutrition - complications</subject><subject>Protein-Energy Malnutrition - physiopathology</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Steatosis</subject><subject>Weaning</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uLEzEUgAdR3LX6D0QHBNGH1tzmEh-EZfFSKCx4ew2ZzEmbJZPUJLO64I83tbNLK_sgeZhw5jtfkpOconiK0QLTBr-59GNw0i623sECYc45ru8Vp5hTMq8JovcP5ifFoxgvEapoW9cPixPCeV3xhp4Wv1ferecJwlAOkGTnrVElaA0qxdLrcpDWjSmYZLx7W67MFYQyJpDJRxNL6frSuDha48oAOZKkU1Bqb63_ady6BBns9dwaDeU2-AR7LvvUTvi4eKCljfBk-s6Kbx_efz3_NF9dfFyen63mquYkzTEimDCCaddwiZqOEiIx9IxqTLHqFOGENS3riOZtniEk60aRCvUNZqoBoLPi-d67tT6KqXBREFRTUtEqm2fFck_0Xl6KbTCDDNfCSyP-BnxYCxmSURaEIl2v24r1rOKMaSZpi5uOEQaaKqr77Ho3rTZ2A_QKXArSHkmP_zizEWt_JWpEWozaLHg1CYL_MeZyicFEBdZKB37c77tBvGqajL74B737dBO1lvkAxmmf11U7qTirWIUR4phmanEHlUcPg1H5lWmT40cJr48SMpPgV1rLMUax_PL5_9mL78fsywN2A9KmTfR23D2ZeAyyPaiCjzGAvi0yRmLXJDfVELsmEVOT5LRnhxd0m3TTFfQPgjMNkQ</recordid><startdate>20180702</startdate><enddate>20180702</enddate><creator>Dalvi, Prasad S</creator><creator>Yang, Steven</creator><creator>Swain, Nathan</creator><creator>Kim, Junsoo</creator><creator>Saha, Senjuti</creator><creator>Bourdon, Celine</creator><creator>Zhang, Ling</creator><creator>Chami, Rose</creator><creator>Bandsma, Robert H J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1298-7220</orcidid></search><sort><creationdate>20180702</creationdate><title>Long-term metabolic effects of malnutrition: Liver steatosis and insulin resistance following early-life protein restriction</title><author>Dalvi, Prasad S ; Yang, Steven ; Swain, Nathan ; Kim, Junsoo ; Saha, Senjuti ; Bourdon, Celine ; Zhang, Ling ; Chami, Rose ; Bandsma, Robert H J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-102124213b79a07b322a1ed43f131cbc2924784b2f9824700a67c250d714c7ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Carbohydrates</topic><topic>Child malnutrition</topic><topic>Children</topic><topic>Chronic illnesses</topic><topic>Complications and side effects</topic><topic>Developing countries</topic><topic>Diabetes</topic><topic>Diet</topic><topic>Diet, Protein-Restricted - 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It is not clear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when they are later in life exposed to a fat and carbohydrate rich obesogenic diet. The lack of knowledge around this dietary "double burden" warrants studies to understand the long-term consequences of children previously exposed to malnutrition. We hypothesized that an early-life nutritional insult of low protein consumption in mice would lead to long-term metabolic disturbances that would exacerbate the development of diet-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD). We investigated the effects of feeding a low protein diet (4% wt/wt) immediately after weaning for four weeks and subsequent feeding of a high carbohydrate high fat feeding for 16 weeks on metabolic function and development of NAFLD. Mice exposed to early-life protein restriction demonstrated a transient glucose intolerance upon recovery by regular chow diet feeding. However, protein restriction after weaning in mice did not exacerbate an obesogenic diet-induced insulin resistance or progression to NAFLD. These data suggest that transient protein restriction in early-life does not exacerbate an obesogenic diet-induced NAFLD and insulin resistance.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29965973</pmid><doi>10.1371/journal.pone.0199916</doi><tpages>e0199916</tpages><orcidid>https://orcid.org/0000-0003-1298-7220</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biology and Life Sciences Carbohydrates Child malnutrition Children Chronic illnesses Complications and side effects Developing countries Diabetes Diet Diet, Protein-Restricted - adverse effects Endocrinology Exposure Famine Fatty change Fatty liver Feeding Female Gene expression Glucose - metabolism Glucose Intolerance - etiology Glucose Intolerance - metabolism Glucose Intolerance - pathology Glucose tolerance Homeostasis Hospitals Inflammation Insulin Insulin Resistance Intolerance Laboratories LDCs Liver Liver diseases Low protein diet Male Malnutrition Medicine Medicine and Health Sciences Metabolic diseases Metabolic disorders Mice Mice, Inbred C57BL Non-alcoholic Fatty Liver Disease - etiology Non-alcoholic Fatty Liver Disease - metabolism Non-alcoholic Fatty Liver Disease - pathology Nutrient deficiency Nutrition research Obesity Protein deficiency Protein-Energy Malnutrition - complications Protein-Energy Malnutrition - physiopathology Proteins Research and Analysis Methods Risk factors Rodents Steatosis Weaning |
| title | Long-term metabolic effects of malnutrition: Liver steatosis and insulin resistance following early-life protein restriction |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T22%3A47%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Long-term%20metabolic%20effects%20of%20malnutrition:%20Liver%20steatosis%20and%20insulin%20resistance%20following%20early-life%20protein%20restriction&rft.jtitle=PloS%20one&rft.au=Dalvi,%20Prasad%20S&rft.date=2018-07-02&rft.volume=13&rft.issue=7&rft.spage=e0199916&rft.epage=e0199916&rft.pages=e0199916-e0199916&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0199916&rft_dat=%3Cgale_plos_%3EA545100913%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2063253521&rft_id=info:pmid/29965973&rft_galeid=A545100913&rft_doaj_id=oai_doaj_org_article_c2bdf854d45944f4a3817b424ef3c3fd&rfr_iscdi=true |