{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T23:29:33Z","timestamp":1769038173460,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,18]],"date-time":"2015-11-18T00:00:00Z","timestamp":1447804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>The plasma concentration of brain natriuretic peptide (BNP) is decreased in obesity, a finding that may be deleterious from a cardiovascular, renal and metabolic standpoint. The present study used a mouse model of high\u2010fructose, high\u2010fat (HFHF) diet and isolated cardiomyocytes to investigate the mechanisms involved in this decrease.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>The gene expression level of BNP is decreased in the left ventricle of mice fed a HFHF diet for 4\u00a0weeks and in cardiomyocytes exposed to prolonged high doses of insulin. A decrease in BNP synthesis may contribute to the decreased BNP plasma concentrations observed in obesity and insulin resistance.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Human studies suggest that insulin resistance and obesity are associated with a decrease in B\u2010type natriuretic peptide (BNP) plasma concentrations. The objective of the study was to gain insights into the mechanisms involved in the association between insulin resistance and decreased BNP plasma concentrations. Mice fed a high\u2010fat, high\u2010fructose (HFHF) diet for 4\u00a0weeks developed mild obesity and systemic insulin resistance. Elevated plasma concentrations of insulin, glucose and triglycerides were noted. The HFHF diet was also associated with myocardial insulin resistance, characterized by an impaired response of the phosphoinositide\u00a03\u2010kinase\u2013AKT (PI3K\u2013AKT) pathway to insulin in the left ventricle. Myocardial BNP expression and protein were decreased in HFHF\u2010fed mice compared with control animals. Exposure of cardiomyocytes to 100\u00a0n<jats:sc>m<\/jats:sc> insulin activated PI3K\u2013AKT signalling (15\u00a0min) and induced a 1.9\u00a0\u00b1\u00a00.3\u2010fold increase in <jats:italic>BNP<\/jats:italic> gene expression (6\u00a0h). Prolonged exposure of cardiomyocytes to a high insulin concentration (100\u00a0n<jats:sc>m<\/jats:sc>) for 48\u00a0h induced insulin resistance, characterized by an impaired response of the PI3K\u2013AKT signalling pathway and a decreased response of the <jats:italic>BNP<\/jats:italic> gene expression to insulin. The decreased response in <jats:italic>BNP<\/jats:italic> gene expression was reproduced by treating cardiomyocytes for 7\u00a0h with a PI3\u2010kinase inhibitor (wortmannin). In conclusion, HFHF diet <jats:italic>in vivo<\/jats:italic>, prolonged exposure to an elevated concentration of insulin or inhibition of the PI3K\u2013AKT pathway <jats:italic>in vitro<\/jats:italic> all decrease <jats:italic>BNP<\/jats:italic> mRNA levels; this decrease may in turn contribute to the decreased BNP peptide concentrations in plasma observed in insulin\u2010resistant individuals.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep085091","type":"journal-article","created":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T09:32:50Z","timestamp":1444296770000},"page":"113-123","source":"Crossref","is-referenced-by-count":10,"title":["Regulation of B\u2010type natriuretic peptide synthesis by insulin in obesity in male mice"],"prefix":"10.1113","volume":"101","author":[{"given":"Haihua","family":"Zhang","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center, Massachusetts General Hospital Harvard Medical School  Boston MA 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Hospital Harvard Medical School  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan Ru","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Vanderbilt University  Nashville TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Vanderbilt University  Nashville TN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marielle","family":"Scherrer\u2010Crosbie","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Massachusetts General Hospital Harvard Medical School  Boston MA USA"},{"name":"Cardiac Ultrasound Laboratory, Cardiology Division, Department of Medicine, Massachusetts General Hospital Harvard Medical School  Boston MA 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