Differences and similarities in hepatic lipogenesis, gluconeogenesis and oxidative imbalance in mice fed diets rich in fructose or sucrose

Schultz, Alini; Barbosa-da-Silva, Sandra; Águila, Márcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

doi:10.1039/c5fo00251f

Cited by 36 publications

(18 citation statements)

References 39 publications

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“…Finally, to regenerate NAD+ and maintain maximal beta-oxidation, obesity increases expression of UCP2 (Chavin et al 1999). Rodents with hepatic steatosis from diets rich in fructose or sucrose also aberrantly overexpress hepatic UCP2 mRNA (Ruiz-Ramirez et al 2011, Schultz et al 2015. These data recommend that transcriptional changes are central to the upregulation of beta-oxidation and ketogenesis in the adaptation to hepatic lipid accumulation.…”

Section: Beta-oxidation and Ketogenesismentioning

confidence: 72%

“…PPARg expression is mainly limited to the adipocyte, but under conditions of chronic hepatic lipid accumulation, the liver expresses considerable amounts of PPARg (VidalPuig et al 1996, Pettinelli & Videla 2011, Schultz et al 2013, Barbosa-da-Silva et al 2015. Both PPARa and PPARg recognize the same fatty acids and eicosanoids ligands (Xu et al 1999).…”

Section: Hepatic Lipids As Signaling Moleculesmentioning

confidence: 99%

“…In both alcohol-and methionine-choline-deficient models of hepatic lipid accumulation, elimination of PPARa signaling increases the resulting hepatic lipid accumulation (Ip et al 2003. Accordingly, PPARa agonist treatment in fatty liver models consistently decreases hepatic steatosis (Ide et al 2004, Larter et al 2012, Barbosa-da-Silva et al 2015, Souza-Mello 2015.…”

Section: Hepatic Lipids As Signaling Moleculesmentioning

confidence: 99%

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Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

Geisler

Renquist

2017

Journal of Endocrinology

156

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Fatty liver can be diet, endocrine, drug, virus or genetically induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting hyperglycemia, hyperlipidemia and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency and elevated sympathetic tone. These endocrine and metabolic changes further encourage hepatic steatosis by regulating adipose tissue lipolysis, liver lipid uptake, de novo lipogenesis (DNL), beta-oxidation, ketogenesis and lipid export. Hepatic lipid accumulation may be induced by 4 separate mechanisms: (1) increased hepatic uptake of circulating fatty acids, (2) increased hepatic de novo fatty acid synthesis, (3) decreased hepatic beta-oxidation and (4) decreased hepatic lipid export. This review will discuss the hormonal regulation of each mechanism comparing multiple physiological models of hepatic lipid accumulation. Nonalcoholic fatty liver disease (NAFLD) is typified by increased hepatic lipid uptake, synthesis, oxidation and export. Chronic hepatic lipid signaling through PPARgamma results in gene expression changes that allow concurrent activity of DNL and beta-oxidation. The importance of hepatic steatosis in driving systemic metabolic dysfunction is highlighted by the common endocrine and metabolic disturbances across many conditions that result in fatty liver. Understanding the mechanisms underlying the metabolic dysfunction that develops as a consequence of hepatic lipid accumulation is critical to identifying points of intervention in this increasingly prevalent disease state.

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Section: Beta-oxidation and Ketogenesismentioning

confidence: 72%

Section: Hepatic Lipids As Signaling Moleculesmentioning

confidence: 99%

Section: Hepatic Lipids As Signaling Moleculesmentioning

confidence: 99%

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Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

Geisler

Renquist

2017

Journal of Endocrinology

156

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“…El stress del RE contribuye a la apoptosis. Finalmente, la progresión de la enfermedad es consecuencia del desbalance entre injuria, reparación y fibrosis (Nguyen & Sanyal, 2012;Schultz et al, 2015).…”

Section: A) Patogénesisunclassified

NAFLD e Ingesta de Fructosa en Altas concentraciones: Una Revisión de la Literatura

Carvallo

Barbosa-da-Silva

et al. 2017

Int. J. Morphol.

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RESUMEN Uno de los endulzantes más comúnmente utilizado es la fructosa. La fructosa es directamente metabolizada en el hígado y se puede transformar en glucosa, posteriormente es almacenada como glicógeno constituyéndose en una fuente de energía para los hepatocitos. Todo el exceso de fructosa se convierte en lípidos ejerciendo un efecto tóxico sobre el hígado, similar al producido por el exceso de alcohol, pudiendo provocar hígado graso no alcohólico (NAFLD). El objetivo de esta revisión es reunir hallazgos recientes en relación al efecto de la ingesta de fructosa en altas concentraciones y su relación con el NAFLD.PALABRAS CLAVE: Hígado graso no alcohólico; esteatohepatitis no alcohólica; fibrosis hepática; Fructosa. INTRODUCCIÓNLa enfermedad hepática por hígado graso no alcohó-lico (NAFLD) es consecuencia de múltiples factores de riesgo como sobrepeso, obesidad central, dislipidemia, resistencia a la insulina y Diabetes Mellitus tipo 2; todos ellos asociados con el síndrome metabólico (Adams et al., 2009). La evolución del NAFLD puede producir esteatohepatitis no alcohólica (NASH), fibrosis hepática y puede predisponer al desarrollo de hepatocarcinoma. El NAFLD se caracteriza por exceso de deposición de lípidos neutros (hepatoesteatosis) en el hígado, más del 5 % de los hepatocitos están almacenando lípidos neutros (ésteres de triglicéridos y colesterol), el depósito de triglicéridos en el hígado es el resultado de un desequilibrio entre la cantidad de energía ingerida y la cantidad usada. El NAFLD comprende un espectro de enfermedad que va desde la estatosis (NAFL) a la esteatohepatitis no alcohólica (NASH) y la fibrosis (Bettermann et al., 2014;Petaja & Yki-Jarvinen, 2016). La ingesta excesiva de grasas y carbohidratos constituye uno de los factores de riesgo de presentar NAFLD. Uno de los endulzantes más comúnmente utilizados en la dieta occidental es la fructosa que es directamente metabolizada en el hígado y se transforma en glucosa, posteriormente es almacenada como glicógeno constituyéndo-se en una fuente de energía para los hepatocitos. Todo el exceso de fructosa se convierte en lípidos ejerciendo un efecto tóxico sobre el hígado, similar al producido por el exceso de alcohol, pudiendo provocar NAFLD (Lustig, 2010). Por tales razones los médicos alientan a sus pacientes a modificar la alimentación, reduciendo el consumo de grasa y carbohidratos simples y a perder el exceso de peso corporal con el fin de prevenir el daño hepático (Lytle & Jump, 2016;Zheng et al., 2016).Actualmente la alta prevalencia de obesidad y Diabetes Mellitus tipo 2 a nivel mundial ha provocado que el NAFLD sea considerado una entidad clínica relevante, constituyendo la principal causa de enfermedad hepática cróni-ca e indicación de trasplante hepático en países desarrollados (Matherly & Puri, 2012).Epidemiología. El NAFLD afecta al 33 % de la población occidental, constituyendo un importante problema de salud pública. Se presenta en el 20-30 % de personas no obesas y 1 Doctorado en Ciencias Morfológicas, Universidad de La Fronte...

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“…Daily foodstuff contains some natural fructose and in recent years foods with considerable refined fructose content have become fairly popular. This is a worrying trend as a high intake of foods rich in fructose is associated with obesity and metabolic problems (5).…”

Section: Introductionmentioning

confidence: 99%

Hypolipidemic effects of flavonoids extracted from Lomatogonium rotatum

Zhang

Wang

2016

Experimental and Therapeutic Medicine

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Abstract. Contained in the Mongolian volumes of Chinese Materia Medica, Lomatogonium rotatum Fries ex Nym. may reduce blood lipid levels and prevent obesity; however, its exact mechanism of action remains unclear. The present study investigated the hypolipidemic and obesity-inhibiting effects of four similarly structured flavonoids extracted from L. rotatum. According to a well-established method, flavonoids such as decussatin were extracted from the whole herb of L. rotatum, and male Wistar rats were subsequently fed a high-fructose diet supplemented with flavonoids (20 mg/kg) for 12 weeks. The levels of total cholesterol, triglyceride (TG), low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol (HDL-C) were detected. In addition, hepatic and epididymal adipose tissues were weighed, and levels of blood glucose, alanine aminotransferase, aspartate aminotransferase, non-esterified fatty acid, insulin and leptin were determined. The mRNA expression levels of fatty acid synthase (FAS) were analyzed using a reverse transcription polymerase chain reaction; whereas FAS, adenosine monophosphate-activated protein kinase (AMPK) and threonine-172 phosphorylated AMPK protein levels were detected by western blotting. The epididymal adipose tissues of rats fed with flavonoids were lighter, as compared with those fed with fructose in the model group. Following a 12-week administration of flavonoids, the serum levels of fasting blood glucose, feeding blood glucose and leptin were decreased. Furthermore, flavonoid treatment reduced TG and cholesterol levels in the blood and increased serum HDL-C levels, as compared with the model group. High-fructose diet administration significantly increased FAS mRNA and protein expression levels, whereas the FAS protein levels of flavonoid-treated rats were markedly reduced.The flavonoid compounds also enhanced threonine-172 phosphorylation of AMPK in the liver lysate, and all flavonoids successfully downregulated leptin levels and the majority decreased the relative weights of epididymal adipose tissue. Therefore, flavonoids may function in a similar way to epigallocatechin gallate, which has previously been shown to inhibit FAS activity by stimulating AMPK in hepatocyte cells via the liver kinase B1 pathway.

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Differences and similarities in hepatic lipogenesis, gluconeogenesis and oxidative imbalance in mice fed diets rich in fructose or sucrose

Abstract: Changes in feeding habits are the primary environmental factors (though modifiable) commonly correlated with increase in diseases such as obesity and associated comorbidities.

Cited by 36 publications

References 39 publications

Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

NAFLD e Ingesta de Fructosa en Altas concentraciones: Una Revisión de la Literatura

Hypolipidemic effects of flavonoids extracted from Lomatogonium rotatum

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