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The Effects of Long-Term High Fat and/or High Sugar Feeding on Sources of Postprandial Hepatic Glycogen and Triglyceride Synthesis in Mice.
Reis-Costa, Ana; Belew, Getachew D; Viegas, Ivan; Tavares, Ludgero C; Meneses, Maria João; Patrício, Bárbara; Gastaldelli, Amalia; Macedo, Maria Paula; Jones, John G.
Afiliação
  • Reis-Costa A; PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal.
  • Belew GD; Center for Neuroscience and Cell Biology (CNC-UC), Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal.
  • Viegas I; Grupo de Estudos de Investigação Fundamental e Translacional (GIFT) da Sociedade Portuguesa de Diabetologia, 1250-198 Lisboa, Portugal.
  • Tavares LC; PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal.
  • Meneses MJ; Center for Neuroscience and Cell Biology (CNC-UC), Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal.
  • Patrício B; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA.
  • Gastaldelli A; Centre for Functional Ecology (CFE), TERRA Associate Laboratory, Department of Life Sciences, University of Coimbra, 3030-790 Coimbra, Portugal.
  • Macedo MP; Vasco da Gama Research Center (CIVG), University School Vasco da Gama, 3020-210 Coimbra, Portugal.
  • Jones JG; iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-082 Lisboa, Portugal.
Nutrients ; 16(14)2024 Jul 09.
Article em En | MEDLINE | ID: mdl-39064628
ABSTRACT

BACKGROUND:

In MASLD (formerly called NAFLD) mouse models, oversupply of dietary fat and sugar is more lipogenic than either nutrient alone. Fatty acids suppress de novo lipogenesis (DNL) from sugars, while DNL inhibits fatty acid oxidation. How such factors interact to impact hepatic triglyceride levels are incompletely understood.

METHODS:

Using deuterated water, we measured DNL in mice fed 18-weeks with standard chow (SC), SC supplemented with 55/45-fructose/glucose in the drinking water at 30% (w/v) (HS), high-fat chow (HF), and HF with HS supplementation (HFHS). Liver glycogen levels and its sources were also measured. For HS and HFHS mice, pentose phosphate (PP) fluxes and fructose contributions to DNL and glycogen were measured using [U-13C]fructose.

RESULTS:

The lipogenic diets caused significantly higher liver triglyceride levels compared to SC. DNL rates were suppressed in HF compared to SC and were partially restored in HFHS but supplied a minority of the additional triglyceride in HFHS compared to HF. Fructose contributed a significantly greater fraction of newly synthesized saturated fatty acids compared to oleic acid in both HS and HFHS. Glycogen levels were not different between diets, but significant differences in Direct and Indirect pathway contributions to glycogen synthesis were found. PP fluxes were similar in HS and HFHS mice and were insufficient to account for DNL reducing equivalents.

CONCLUSIONS:

Despite amplifying the lipogenic effects of fat, the fact that sugar-activated DNL per se barely contributes suggests that its role is likely more relevant in the inhibition of fatty acid oxidation. Fructose promotes lipogenesis of saturated over unsaturated fatty acids and contributes to maintenance of glycogen levels. PP fluxes associated with sugar conversion to fat account for a minor fraction of DNL reducing equivalents.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Triglicerídeos / Período Pós-Prandial / Lipogênese / Dieta Hiperlipídica / Frutose / Fígado / Glicogênio Hepático / Camundongos Endogâmicos C57BL Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Triglicerídeos / Período Pós-Prandial / Lipogênese / Dieta Hiperlipídica / Frutose / Fígado / Glicogênio Hepático / Camundongos Endogâmicos C57BL Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article