Liver denervation affects hepatocyte mitochondrial fatty acid transport capacity

Carreño, Flávia Regina; Seelaender, Marília

doi:10.1002/cbf.1047

Cited by 31 publications

(26 citation statements)

References 47 publications

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“…The activity of the enzyme CPT I is the principal site of regulation of oxidation. 44 A decrease in the expression of this enzyme in denervated animals is herein reported, in agreement with our previous results that showed a decrease in the activity of this enzyme, 20 reducing the availability of fatty acids for oxidation. Therefore, in denervated animals, these fatty acids are available to follow other pathways, as for instance, the synthesis of cholesterol, as we demonstrated a slight increase in hepatic cholesterol concentration, related to the altered expression of ACAT.…”

Section: Discussionsupporting

confidence: 95%

“…4,25 Previous studies in our laboratory had already shown that hepatic denervation alters lipid metabolism in the organ, leading towards lower oxidation of fatty acids and decreased incorporation into VLDL. 20 It is known that catecholamines play a role in the regulation of VLDL secretion, 17,19,26 but no studies, to our knowledge, have so far examined the importance and contribution of the sympathetic innervation to the process. Our results show a lower secretion of VLDL in the denervated animals compared with controls, which was related with a lower expression of apoB in these.…”

Section: Discussionmentioning

confidence: 99%

“…Shamoperated animals were submitted to the same surgical procedures, with the application of 9% NaCl solution onto the structures, in substitution for phenol. All experiments were carried out on the 7 th day after the procedure (see 20 ).…”

Section: Denervation Protocolmentioning

confidence: 99%

“…19 A previous study by our group demonstrated decreased capacity of fatty acid oxidation and the incorporation of lipid in the VLDL secreted by denervated livers. 20 As it is clear that the hepatic sympathetic innervation is markedly involved in the control of liver metabolism (as reported mainly by researchers addressing carbohydrate metabolism) and physiology, we sought to examine its influence upon VLDL secretion. This is one of the first attempts, to our knowledge and surprise, to investigate one such important relationship, considering, for instance, the implications for liver transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Hepatic denervation impairs the assembly and secretion of VLDL‐TAG

Tavares

Seelaender

2008

Cell Biochemistry & Function

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VLDL secretion is a regulated process that depends on the availability of lipids, apoB and MTP. Our aim was to investigate the effect of liver denervation upon the secretion of VLDL and the expression of proteins involved in this process. Denervation was achieved by applying a 85% phenol solution onto the portal tract, while control animals were treated with 9% NaCl. VLDL secretion was evaluated by the Tyloxapol method. The hepatic concentration of TAG and cholesterol, and the plasma concentration of TAG, cholesterol, VLDL-TAG, VLDL-cholesterol and HDL-cholesterol were measured, as well as mRNA expression of proteins involved in the process of VLDL assembly. Hepatic acinar distribution of MTP and apoB was evaluated by immunohistochemistry. Denervation increased plasma concentration of cholesterol (125.3 +/- 10.1 vs. 67.1 +/- 4.9 mg dL(-1)) and VLDL-cholesterol (61.6 +/- 5.6 vs. 29.4 +/- 3.3 mg dL(-1)), but HDL-cholesterol was unchanged (45.5 +/- 6.1 vs. 36.9 +/- 3.9 mg dL(-1)). Secretion of VLDL-TAG (47.5 +/- 23.8 vs. 148.5 +/- 27.4 mg dL h(-1)) and mRNA expression of CPT I and apoB were reduced (p < 0.01) in the denervated animals. MTP and apoB acinar distribution was not altered in the denervated animals, but the intensity of the reaction was reduced in relation to controls.

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Section: Discussionsupporting

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Denervation Protocolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatic denervation impairs the assembly and secretion of VLDL‐TAG

Tavares

Seelaender

2008

Cell Biochemistry & Function

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“…Importantly, also central GLP-1 infusion decreased hepatic TG content and expression of lipogenic enzymes in mice, suggesting that GLP-1 can at least in part affect hepatic TG metabolism via a central mechanism ( 38,39 ). In addition, in vitro activation reduced incorporation of exogenously administered fatty acids into the plasma VLDL-TG fraction ( 27 ), pointing to decreased VLDL-TG secretion. Accordingly, Bruinstroop et al ( 28 ) recently showed that hepatic sympathetic denervation in rats reduced hepatic VLDL-TG secretion.…”

Section: Anatomy Of Hypothalamic Sympathetic Outflowmentioning

confidence: 95%

Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies

Geerling

Boon

Kooijman

et al. 2014

Journal of Lipid Research

107

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Dyslipidemia is one of the classical risk factors for cardiovascular diseases (CVD) besides hypertension, type 2 diabetes, and smoking ( 1 ). Dyslipidemia is defi ned as an elevation of plasma LDL-cholesterol (LDL-C), triglycerides (TG), or both, with or without a lowering of HDLcholesterol (HDL-C) ( 2 ). Whereas elevated LDL-C is a well-established major predictor of CVD and has been the primary target for lipid-lowering strategies, evidence suggests that an elevated TG level is an independent risk factor for CVD development as well ( 3, 4 ). Plasma TG levels are considered elevated when they exceed 150 mg/dl, which is observed in 31% of the adult US population ( 5 ). Although hypertriglyceridemia can be caused by rare monogenic disorders, it is mostly caused by a complex interaction between environmental factors and subtle variations in genes involved in lipoprotein metabolism ( 5 ). Current treatments for hypertriglyceridemia are aimed at either increasing TG clearance (e.g., fi brates) ( 6 ) or at decreasing lipolysis in WAT (e.g., niacin) ( 7 ). In addition, reduction of VLDL-TG production lowers plasma TG levels (e.g., exendin-4) ( 8 ).In recent years, the autonomic nervous system, which consists of a sympathetic and a parasympathetic branch, emerged as an important regulator of metabolic homeostasis. Whereas the role of the sympathetic nervous system (SNS) in the regulation of glucose metabolism has been fi rmly established (for review, see Ref. 9 ), considerably fewer studies have focused on its role in TG metabolism. This review provides an update specifi cally on the role of Abstract Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels. Interestingly, recent evidence points to a prominent role of the hypothalamus in TG metabolism through innervating the liver, WAT, and BAT mainly via sympathetic branches of the autonomic nervous system. Here, we review the recent fi ndings in the area of sympathetic control of TG metabolism. Various neuronal populations, such as neuropeptide Y (NPY)-expressing neurons and melanocortin-expressing neurons, as well as peripherally produced hormones (i.e., GLP-1, leptin, and insulin), modulate sympathetic outfl ow from the hypothalamus toward target organs and thereby infl uence peripheral TG metabolism. We conclude that sympathetic stimulation in general increases lipolysis in WAT, enhances VLDL-TG production by the liver, and increases the activity of BAT with respect to lipolysis of TG, followed by combustion of fatty acids toward heat. Moreover, the increased knowledge about the involvement of the neuroendocrine system in TG metabolism presented in this review offers new therapeutic options to fi ght hypertriglyceridemia by specifi cally modulating sympathetic nervous system outfl ow toward liver, BAT, or WAT .-Geerling, J. J., M. R. B...

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The Sympathetic‐Immune Milieu in Metabolic Health and Diseases: Insights from Pancreas, Liver, Intestine, and Adipose Tissues

Ren,

Hua,

Cao

et al. 2023

Advanced Science

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Sympathetic innervation plays a crucial role in maintaining energy balance and contributes to metabolic pathophysiology. Recent evidence has begun to uncover the innervation landscape of sympathetic projections and sheds light on their important functions in metabolic activities. Additionally, the immune system has long been studied for its essential roles in metabolic health and diseases. In this review, the aim is to provide an overview of the current research progress on the sympathetic regulation of key metabolic organs, including the pancreas, liver, intestine, and adipose tissues. In particular, efforts are made to highlight the critical roles of the peripheral nervous system and its potential interplay with immune components. Overall, it is hoped to underscore the importance of studying metabolic organs from a comprehensive and interconnected perspective, which will provide valuable insights into the complex mechanisms underlying metabolic regulation and may lead to novel therapeutic strategies for metabolic diseases.

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Liver denervation affects hepatocyte mitochondrial fatty acid transport capacity

Cited by 31 publications

References 47 publications

Hepatic denervation impairs the assembly and secretion of VLDL‐TAG

Hepatic denervation impairs the assembly and secretion of VLDL‐TAG

Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies

The Sympathetic‐Immune Milieu in Metabolic Health and Diseases: Insights from Pancreas, Liver, Intestine, and Adipose Tissues

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