title: Application of an In Vivo Hepatic Triacylglycerol Production Method in the Setting of a High-Fat Diet in Mice.
abstract: 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-including the impact on food intake, energy balance, and weight gain-have 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 7-10 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 7-10 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.
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA. kdonomoore@uams.edu.
authors.forename: Kikumi D
authors.initials: KD
authors.lastname: Ono-Moore
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA. FergusonME@archildrens.org.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ferguson
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA. BlackburnMichaelL@uams.edu.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA. BlackburnMichaelL@uams.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blackburn
authors.affiliation: XOMA Corporation, Berkeley, CA 94710, USA. hassan.issafras@merck.com.
authors.forename: Hassan
authors.initials: H
authors.lastname: Issafras
authors.affiliation: Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA. shadams@uams.edu.|Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA. shadams@uams.edu.
authors.forename: Sean H
authors.initials: SH
authors.lastname: Adams
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D002149:Energy Intake; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000209:etiology; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000209:etiology; D014280:Triglycerides / Q000096:biosynthesis* / Q000097:blood; D015430:Weight Gain
chemical_list: D005230:Fatty Acids, Nonesterified; D014280:Triglycerides
keywords: DIO; fatty acid synthase; high fat; non-alcoholic fatty liver disease; poloxamer 407; triacylglycerols