{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:32:26Z","timestamp":1773315146580,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Ectopic liver fat deposition, resulting from impaired subcutaneous adipose tissue expandability, may represent an age-dependent key feature linking low birth weight (LBW) with increased risk of type 2 diabetes (T2D). We examined whether presumably healthy early middle-aged, non-obese LBW subjects exhibit increased liver fat content, whether increased liver fat in LBW is associated with the severity of dysmetabolic traits and finally whether such associations may be confounded by genetic factors.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Using <jats:sup>1<\/jats:sup>H magnetic resonance spectroscopy, we measured hepatic fat content in 26 early middle-aged, non-obese LBW and 22 BMI-matched normal birth weight (NBW) males. Endogenous glucose production was measured by stable isotopes, and a range of plasma adipokine and gut hormone analytes were measured by multiplex ELISA. Genetic risk scores were calculated from genome-wide association study (GWAS) data for birth weight, height, T2D, plasma cholesterol and risk genotypes for non-alcoholic fatty liver disease (NAFLD).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The LBW subjects had significantly increased hepatic fat content compared with NBW controls (<jats:italic>P<\/jats:italic>= 0.014), and 20% of LBW vs no controls had overt NAFLD. LBW subjects with NAFLD displayed widespread metabolic changes compared with NBW and LBW individuals without NAFLD, including hepatic insulin resistance, plasma adipokine and gut hormone perturbations as well as dyslipidemia. As an exception, plasma adiponectin levels were lower in LBW subjects both with and without NAFLD as compared to NBW controls. Genetic risk for selected differential traits did not differ between groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Increased liver fat content including overt NAFLD may be on the critical path linking LBW with increased risk of developing T2D in a non-genetic manner.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-1221","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T14:57:10Z","timestamp":1645801030000},"page":"511-521","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":19,"title":["Increased liver fat associates with severe metabolic perturbations in low birth weight men"],"prefix":"10.1093","volume":"186","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6653-9020","authenticated-orcid":true,"given":"Charlotte","family":"Br\u00f8ns","sequence":"first","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Cathrine Baun","family":"Thuesen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Line Ohrt","family":"Elingaard-Larsen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Justesen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus Tanderup","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolai Stevns","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helene B\u00e6k","family":"Juel","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"St\u00f8rling","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Ried-Larsen","sequence":"additional","affiliation":[{"name":"Centre for Physical Activity Research (CFAS), Rigshospitalet, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren M","family":"Sparks","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Advent Health, Orlando, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerrit","family":"van Hall","sequence":"additional","affiliation":[{"name":"Clinical Metabolomics Core Facility, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Else Rub\u00e6k","family":"Danielsen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torben","family":"Hansen","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Vaag","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen, Herlev, Denmark"},{"name":"Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1007\/s00125-012-2589-y","article-title":"The thrifty phenotype hypothesis revisited","volume":"55","author":"Vaag","year":"2012","unstructured":"Vaag AAGrunnet LGArora GPBr\u00f8ns C. 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