{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:27:21Z","timestamp":1791916041968,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2016,12,28]],"date-time":"2016-12-28T00:00:00Z","timestamp":1482883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"USDA-ARS Project","award":["6026-51000-010-05S"],"award-info":[{"award-number":["6026-51000-010-05S"]}]},{"name":"XOMA Corp.","award":["CRADA 58-3K95-1-1497"],"award-info":[{"award-number":["CRADA 58-3K95-1-1497"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>High-fat (HF) diets typically promote diet-induced obesity (DIO) and metabolic dysfunction (i.e., insulin resistance, hypertriglyceridemia, and hepatic steatosis). Dysfunction of triacylglycerol (TAG) metabolism may contribute to the development of hepatic steatosis, via increased de novo lipogenesis or repackaging of circulating nonesterified fatty acids (NEFAs). Hepatic TAG production (HTP) rate can be assessed through injecting mice with nonionic detergents that inhibit tissue lipoprotein lipase. Potential confounding effects of detergent-based HTP tests (HTPTs) used in longitudinal studies\u2014including the impact on food intake, energy balance, and weight gain\u2014have not been reported. To examine this, male C57BL\/6J mice were fed a 10% or 60% kcal diet. After 4 weeks, the mice underwent an HTPT via poloxamer 407 intraperitoneal injections (1000 mg\/kg). Weight gain, energy intake, and postabsorptive TAG levels normalized 7\u201310 days post-HTPT. The post-HTPT recovery of body weight and energy intake suggest that, in metabolic phenotyping studies, any additional sample collection should occur at least 7\u201310 days after the HTPT to reduce confounding effects. Diet-specific effects on HTP were also observed: HF-fed mice had reduced HTP, plasma TAG, and NEFA levels compared to controls. In conclusion, the current study highlights the procedural and physiological complexities associated with studying lipid metabolism using a HTPT in the DIO mouse model.<\/jats:p>","DOI":"10.3390\/nu9010016","type":"journal-article","created":{"date-parts":[[2016,12,28]],"date-time":"2016-12-28T11:22:14Z","timestamp":1482924134000},"page":"16","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Application of an In Vivo Hepatic Triacylglycerol Production Method in the Setting of a High-Fat Diet in Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Kikumi","family":"Ono-Moore","sequence":"first","affiliation":[{"name":"Arkansas Children\u2019s Nutrition Center, Little Rock, AR 72202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Arkansas Children\u2019s Nutrition Center, Little Rock, AR 72202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Arkansas Children\u2019s Nutrition Center, Little Rock, AR 72202, USA"},{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Issafras","sequence":"additional","affiliation":[{"name":"XOMA Corporation, Berkeley, CA 94710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Adams","sequence":"additional","affiliation":[{"name":"Arkansas Children\u2019s Nutrition Center, Little Rock, AR 72202, USA"},{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1007\/s00125-015-3525-8","article-title":"Pathophysiology of diabetic dyslipidaemia: Where are we?","volume":"58","author":"Verges","year":"2015","journal-title":"Diabetologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1053\/gast.2001.23256","article-title":"Nonalcoholic steatohepatitis: Association of insulin resistance and mitochondrial abnormalities","volume":"120","author":"Sanyal","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00535-013-0758-5","article-title":"Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease","volume":"48","author":"Kawano","year":"2013","journal-title":"J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.2337\/diab.37.9.1163","article-title":"Diet-induced type II diabetes in C57BL\/6J mice","volume":"37","author":"Surwit","year":"1988","journal-title":"Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.3945\/jn.110.127068","article-title":"Inflammatory phenotyping identifies CD11d as a gene markedly induced in white adipose tissue in obese rodents and women","volume":"141","author":"Thomas","year":"2011","journal-title":"J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1743-7075-9-3","article-title":"A high calcium diet containing nonfat dry milk reduces weight gain and associated adipose tissue inflammation in diet-induced obese mice when compared to high calcium alone","volume":"9","author":"Thomas","year":"2012","journal-title":"Nutr. Metab. (Lond.)"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.2337\/db14-0804","article-title":"Dipeptidyl peptidase-4 inhibition ameliorates Western diet-induced hepatic steatosis and insulin resistance through hepatic lipid remodeling and modulation of hepatic mitochondrial function","volume":"64","author":"Aroor","year":"2015","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21240","DOI":"10.3390\/ijms141121240","article-title":"Lessons from mouse models of high-fat diet-induced NAFLD","volume":"14","author":"Nakamura","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.2337\/db16-0236","article-title":"Fasting Plasma insulin concentrations are associated with changes in hepatic fatty acid synthesis and partitioning prior to changes in liver fat content in healthy adults","volume":"65","author":"Pramfalk","year":"2016","journal-title":"Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1194\/jlr.D500019-JLR200","article-title":"Determining hepatic triglyceride production in mice: Comparison of poloxamer 407 with Triton WR-1339","volume":"46","author":"Millar","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_11","first-page":"192","article-title":"Poloxamer 407-mediated changes in plasma cholesterol and triglycerides following intraperitoneal injection to rats","volume":"46","author":"Wout","year":"1992","journal-title":"J. Parenter. Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0021-9150(97)00193-7","article-title":"Poloxamer 407-induced atherogenesis in the C57BL\/6 mouse","volume":"136","author":"Palmer","year":"1998","journal-title":"Atherosclerosis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"G27","DOI":"10.1152\/ajpgi.00296.2007","article-title":"A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet","volume":"294","author":"Baumgardner","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/brv.12178","article-title":"De novo lipogenesis in the liver in health and disease: More than just a shunting yard for glucose","volume":"91","author":"Sanders","year":"2016","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2337\/diabetes.51.4.1233","article-title":"Hepatic expression of microsomal triglyceride transfer protein and in vivo secretion of triglyceride-rich lipoproteins are increased in obese diabetic mice","volume":"51","author":"Bartels","year":"2002","journal-title":"Diabetes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1172\/JCI6576","article-title":"Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice","volume":"103","author":"Raabe","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hirahatake, K.M., Meissen, J.K., Fiehn, O., and Adams, S.H. (2011). Comparative effects of fructose and glucose on lipogenic gene expression and intermediary metabolism in HepG2 liver cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026583"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1257S","DOI":"10.3945\/jn.108.098186","article-title":"Dietary fructose and glucose differentially affect lipid and glucose homeostasis","volume":"139","author":"Schaefer","year":"2009","journal-title":"J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.bbalip.2011.09.017","article-title":"Fatty acid synthase and liver triglyceride metabolism: Housekeeper or messenger?","volume":"1821","author":"Semenkovich","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1093\/jn\/131.8.2074","article-title":"Insulin stimulation of hepatic triacylglycerol secretion and the etiology of insulin resistance","volume":"131","author":"Zammit","year":"2001","journal-title":"J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1042\/CS20070115","article-title":"Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome","volume":"114","author":"Aguilera","year":"2008","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI23621","article-title":"Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease","volume":"115","author":"Donnelly","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1211\/jpp.58.8.0011","article-title":"Inhibition of pancreatic lipase by poloxamer 407 may provide an adjunct treatment strategy for weight loss","volume":"58","author":"Johnston","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_25","first-page":"189","article-title":"Poloxamer 407-mediated alterations in the activities of enzymes regulating lipid metabolism in rats","volume":"6","author":"Wasan","year":"2003","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1073\/pnas.1423952112","article-title":"Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids","volume":"112","author":"Vatner","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ronis, M., Mercer, K., Engi, B., Pulliam, C., Zimniak, P., Hennings, L., Shearn, C., Badger, T., and Petersen, D. (2016). Global deletion of glutathione S-Transferase A4 exacerbates developmental N 1 onalcoholic steatohepatitis. Am. J. Pathol.","DOI":"10.1016\/j.ajpath.2016.10.022"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1042\/bj1290439","article-title":"Fatty acid synthetase activity in the liver and adipose tissue of rats fed with various carbohydrates","volume":"129","author":"Bruckdorfer","year":"1972","journal-title":"Biochem. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1096\/fasebj.8.1.7905448","article-title":"Regulation of lipogenic enzyme gene expression by nutrients and hormones","volume":"8","author":"Girard","year":"1994","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.bbadis.2008.02.007","article-title":"Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver","volume":"1782","author":"Koo","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1753-4887.2005.tb00132.x","article-title":"Dietary fructose: Implications for dysregulation of energy homeostasis and lipid\/carbohydrate metabolism","volume":"63","author":"Havel","year":"2005","journal-title":"Nutr. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15597","DOI":"10.1073\/pnas.0405238101","article-title":"Carbohydrate response element binding protein directly promotes lipogenic enzyme gene transcription","volume":"101","author":"Ishii","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1194\/jlr.M052308","article-title":"A high-fat diet suppresses de novo lipogenesis and desaturation but not elongation and triglyceride synthesis in mice","volume":"55","author":"Duarte","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Oosterveer, M.H., van Dijk, T.H., Tietge, U.J., Boer, T., Havinga, R., Stellaard, F., Groen, A.K., Kuipers, F., and Reijngoud, D.J. (2009). High fat feeding induces hepatic fatty acid elongation in mice. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006066"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3530","DOI":"10.2337\/diabetes.54.12.3530","article-title":"Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL\/6 mice","volume":"54","author":"Park","year":"2005","journal-title":"Diabetes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1007\/s00125-013-2913-1","article-title":"Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding","volume":"56","author":"Turner","year":"2013","journal-title":"Diabetologia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"32345","DOI":"10.1074\/jbc.M313478200","article-title":"Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease","volume":"279","author":"Samuel","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"673","DOI":"10.4254\/wjh.v8.i16.673","article-title":"Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy","volume":"8","author":"Kristiansen","year":"2016","journal-title":"World J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1053\/j.gastro.2013.11.049","article-title":"Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease","volume":"146","author":"Lambert","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1053\/j.gastro.2007.11.038","article-title":"Alterations in adipose tissue and hepatic lipid kinetics in obese men and women with nonalcoholic fatty liver disease","volume":"134","author":"Fabbrini","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/ajcn\/77.1.43","article-title":"Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets","volume":"77","author":"Schwarz","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3109\/10409231003667500","article-title":"Genetic control of de novo lipogenesis: Role in diet-induced obesity","volume":"45","author":"Strable","year":"2010","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1172\/JCI118645","article-title":"Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet","volume":"97","author":"Hudgins","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1093\/aje\/kws264","article-title":"Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: A meta-analysis of randomized controlled clinical trials","volume":"176","author":"Hu","year":"2012","journal-title":"Am. J. Epidemiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/1\/16\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:29:25Z","timestamp":1760210965000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/1\/16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,28]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,1]]}},"alternative-id":["nu9010016"],"URL":"https:\/\/doi.org\/10.3390\/nu9010016","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,28]]}}}