ChREBP Rather Than SHP Regulates Hepatic VLDL Secretion

Niwa, Hiroyuki; Iizuka, Katsumi; Kato, Takehiro; Wu, Wudelehu; Tsuchida, Hiromi; Takao, Ken; Horikawa, Yukio; Takeda, Jun

doi:10.3390/nu10030321

Cited by 24 publications

(32 citation statements)

References 49 publications

(110 reference statements)

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“…For humans and mice, however, MTTP deficiency can result in hypolipidemia and fatty liver disease. 23 MTTP caused no significant changes in the protein level in our study, although the mRNA level decreased. ApoE is a component of VLDL particles secreted from the liver.…”

Section: Discussioncontrasting

confidence: 66%

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Angiopoietin‐like protein 4 promotes very‐low‐density lipoprotein assembly and secretion in bovine hepatocytes in vitro

et al. 2020

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In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin‐like protein 4 (ANGPTL4) is a well‐known downstream target of peroxisome proliferator‐activated receptors (PPARs), which regulate the glucose and fatty acid metabolisms. The inhibition of lipoprotein lipase (LPL) activity interferes with the storage of triglycerides (TG) in adipocytes, which plays an essential role in lipid metabolism in rodents. However, it remains unclear whether ANGPTL4 is involved in the pathological process of fatty liver in dairy cows as a result of the regulation of the hepatocellular lipid transport system. This study intended to investigate the effect of ANGPTL4 on the very‐low‐density lipoprotein (VLDL) assembly and secretion in bovine hepatocytes. Bovine hepatocytes were isolated using a modified two‐step perfusion and collagenase digestion process, and treated with different concentrations of ANGPTL4 (0, 4, 12, and 24 ng/ml) for 24 hr. The results showed that a high concentration of ANGPTL4 could significantly increase the extracellular concentration of VLDL while reducing the intracellular content of TG. Thus, it was confirmed that ANGPTL4 could promote the transport of TG in the form of VLDL by partially regulating the expression of related proteins in hepatocytes, thereby contributing to the partial adaptive regulation of lipid transport in dairy cows.

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Section: Discussioncontrasting

confidence: 66%

“…MTTP is essential for ApoB‐containing lipoproteins in terms of assembly and secretion purposes. For humans and mice, however, MTTP deficiency can result in hypolipidemia and fatty liver disease 23 . MTTP caused no significant changes in the protein level in our study, although the mRNA level decreased.…”

Section: Discussioncontrasting

confidence: 59%

Angiopoietin‐like protein 4 promotes very‐low‐density lipoprotein assembly and secretion in bovine hepatocytes in vitro

et al. 2020

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“…Total RNA isolation, cDNA synthesis, and real-time PCR analysis were performed as described [ 22 , 23 , 29 , 30 , 31 ]. Equal amounts of RNA from six mice were pooled and cDNA was synthesized.…”

Section: Methodsmentioning

confidence: 99%

ChREBP Reciprocally Regulates Liver and Plasma Triacylglycerol Levels in Different Manners

et al. 2018

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Carbohydrate response element-binding protein (ChREBP) has an important role in the carbohydrate-mediated regulation of hepatic de novo lipogenesis, but the mechanism for how it regulates plasma triacylglycerol (TAG) levels has not been established. This study aimed to clarify the role of ChREBP in regulation of plasma TAG levels. We analyzed the metabolic changes in mice infected with an adenovirus expressing ChREBP Δ196 (Ad-ChREBP). Compared with adenovirus harboring green fluorescent protein infected mice, Ad-ChREBP-infected mice had higher plasma free fatty acid levels and paradoxically lower plasma 3-hydroxybutyrate levels through decreased fatty acid oxidation, rather than ketogenesis. Consistent with their hepatomegaly and increased lipogenic gene expression, the liver TAG contents were much higher. Regarding lipid composition, C16:0 was much lower and C18:1n-9 was much higher, compatible with increased stearoyl CoA desaturase-1 and ELOVL fatty acid elongase 6 expression. Furthermore, Ad-ChREBP-infected mice had decreased plasma TAG and very low density lipoprotein (VLDL)-TAG levels, consistent with decreased Angiopoietin-like protein 3 (Angptl3) and increased fibroblast growth factor (Fgf21) mRNA and protein levels. Finally, Ad-ChREBP infection increased white adipose tissue Ucp1 mRNA levels with increased plasma Fgf21 levels. Because Fgf21 and Angptl3 are known to activate and suppress lipolysis in adipose tissues and oxidative tissues, ChREBP appears to regulate plasma TAG levels by modulating Fgf21 and Angptl3 levels. Thus, ChREBP overexpression led to dissociation of hepatic steatosis from hyperlipidemia.

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“…Indeed, in response to increased glucose concentration, ChREBP is translocated to the nucleus and it activates several genes involved in glucose and lipid metabolism [such as liver-Pyruvate kinase (L-PK), Fatty Acid Synthase (FAS) acetyl-CoA carboxylase (ACC), and stearoyl-CoA desaturase (SCD1)], but also genes involved in insulin signaling [27][28][29]. Recently, ChREBP was pointed out as a potential regulator of VLDL secretion in the liver [30]. Thus, it is assumed that ChREBP has important roles in the development of liver diseases including NAFLD [31].…”

Section: Chrebp: a Glucose Sensormentioning

confidence: 99%

Glucose-6 Phosphate, a Central Hub for Liver Carbohydrate Metabolism

2019

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Cells efficiently adjust their metabolism according to the abundance of nutrients and energy. The ability to switch cellular metabolism between anabolic and catabolic processes is critical for cell growth. Glucose-6 phosphate is the first intermediate of glucose metabolism and plays a central role in the energy metabolism of the liver. It acts as a hub to metabolically connect glycolysis, the pentose phosphate pathway, glycogen synthesis, de novo lipogenesis, and the hexosamine pathway. In this review, we describe the metabolic fate of glucose-6 phosphate in a healthy liver and the metabolic reprogramming occurring in two pathologies characterized by a deregulation of glucose homeostasis, namely type 2 diabetes, which is characterized by fasting hyperglycemia; and glycogen storage disease type I, where patients develop severe hypoglycemia during short fasting periods. In these two conditions, dysfunction of glucose metabolism results in non-alcoholic fatty liver disease, which may possibly lead to the development of hepatic tumors. Moreover, we also emphasize the role of the transcription factor carbohydrate response element-binding protein (ChREBP), known to link glucose and lipid metabolisms. In this regard, comparing these two metabolic diseases is a fruitful approach to better understand the key role of glucose-6 phosphate in liver metabolism in health and disease.

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ChREBP Rather Than SHP Regulates Hepatic VLDL Secretion

Cited by 24 publications

References 49 publications

Angiopoietin‐like protein 4 promotes very‐low‐density lipoprotein assembly and secretion in bovine hepatocytes in vitro

Angiopoietin‐like protein 4 promotes very‐low‐density lipoprotein assembly and secretion in bovine hepatocytes in vitro

ChREBP Reciprocally Regulates Liver and Plasma Triacylglycerol Levels in Different Manners

Glucose-6 Phosphate, a Central Hub for Liver Carbohydrate Metabolism

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