ATP synthesis and storage

Bonora, Massimo; Patergnani, Simone; Rimessi, Alessandro; Marchi, Elena De; Suski, Jan M.; Bononi, Angela; Giorgi, Carlotta; Marchi, Saverio; Missiroli, Sonia; Poletti, Federica; Wieckowski, Mariusz R.; Pinton, Paolo

doi:10.1007/s11302-012-9305-8

Cited by 370 publications

(238 citation statements)

References 137 publications

(141 reference statements)

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“…Once chylomicrons or VLDL arrive in the circulation, lipoprotein lipase (LPL) present on the capillary beds of adipose tissue and muscle hydrolyze TG into glycerol and FFA. The liberated FFA can subsequently be taken up by white adipocytes to be stored as TG or by muscle cells and brown adipocytes to be combusted toward ATP and heat, respectively ( 12,13 ). Cellular uptake of FFA is mediated by various cell surface receptors, including FA transport proteins and CD36 ( 14 ).…”

Section: Metabolism Of Triglyceride-rich Lipoproteinsmentioning

confidence: 99%

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

Geerling

Boon

Kooijman

et al. 2014

Journal of Lipid Research

105

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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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Section: Metabolism Of Triglyceride-rich Lipoproteinsmentioning

confidence: 99%

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

Geerling

Boon

Kooijman

et al. 2014

Journal of Lipid Research

105

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“…Figure 1 illustrates the metabolic processes involved in energy production in a muscle cell and the concept of energy continuum during physical activity. In humans, chemical energy is available in the form of ATP, which is generated by two energy systems: anaerobic and aerobic (Bonora et al 2012). The anaerobic energy system relies on preformed ATP as phosphocreatine (PCr) stores or ATP production from anaerobic glycolysis, i.e.…”

Section: Bioenergetics In Skeletal Musclementioning

confidence: 99%

Action of GH on skeletal muscle function: molecular and metabolic mechanisms

Chikani

2013

Journal of Molecular Endocrinology

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Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports and muscle function in the elderly. This paper critically reviews information on the effects of GH on muscle function covering structure, protein metabolism, the role of IGF1 mediation, bioenergetics and performance drawn from molecular, cellular and physiological studies on animals and humans. GH increases muscle strength by enhancing muscle mass without affecting contractile force or fibre composition type. GH stimulates whole-body protein accretion with protein synthesis occurring in muscular and extra-muscular sites. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. GH exerts complex multi-system effects on skeletal muscle function in part mediated by the IGF system.

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“…Meanwhile, Ca 2 þ accumulation in the mitochondrial matrix requires close morphofunctional coupling between Ca 2 þ stores and the mitochondrial Ca 2 þ uniporter (MCU) complex in the inner membrane 12 . The fine modulation of mitochondrial Ca 2 þ homeostasis has a fundamental role in many processes that preserve cellular viability, including ATP metabolism 13 , mitophagy 14 and apoptosis 15 . When mitochondrial Ca 2 þ homeostasis is compromised, various pathological conditions can occur, such as inflammation 16 , mitochondrial diseases 17 and cancer 18 .…”

mentioning

confidence: 99%

Mitochondrial Ca2+-dependent NLRP3 activation exacerbates the Pseudomonas aeruginosa-driven inflammatory response in cystic fibrosis

et al. 2015

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The common pathological manifestation of cystic fibrosis (CF) is associated with an excessive lung inflammatory response characterized by interleukin-1b accumulation. CF airway epithelial cells show an exacerbated pro-inflammatory response to Pseudomonas aeruginosa; however, it is unclear whether this heightened inflammatory response is intrinsic to cells lacking CF transmembrane conductance regulator (CFTR). Here we demonstrate that the degree and quality of the inflammatory response in CF are supported by P. aeruginosadependent mitochondrial perturbation, in which flagellin is the inducer and mitochondrial Ca 2 þ uniporter (MCU) is a signal-integrating organelle member for NLRP3 activation and IL-1b and IL-18 processing. Our work elucidates the regulation of the NLRP3 inflammasome by mitochondrial Ca 2 þ in the P. aeruginosa-dependent inflammatory response and deepens our understanding of the significance of mitochondria in the Ca 2 þ -dependent control of inflammation. hronic airway infection by Pseudomonas aeruginosa is a common pathological manifestation in cystic fibrosis (CF) patients, and the role of calcium ions (Ca 2 þ ) in this process seems pivotal in controlling the P. aeruginosa-dependent innate immune response 1 . This manifestation is associated with an excessive inflammatory response characterized by the accumulation of large amounts of cytokines, including interleukin-1b (IL-1b) 2 .Previous studies support the role of IL-1b in the pathogenesis of CF inflammatory lung disease. The levels of IL-1b are increased in bronchoalveolar lavage fluid of CF patients 2,3 , and polymorphisms in the IL-1b gene have been associated with varying degrees of disease severity 4 .The maturation of IL-1b and IL-18 are directed by the caspase-1 (casp-1)-activating multiprotein platform, the inflammasome. Four distinct inflammasomes that contain a nucleotidebinding and oligomerization domain (NOD)-like receptor have been identified: NLRP1, IPAF, NLRP3 and AIM2 (ref. 5). NODlike receptors (NLRs) are intracellular pattern-recognition receptors that recognize pathogen-associated molecular patterns and activate the pro-inflammatory response through specific pathways 6 . It is generally accepted that the release of IL-1b and IL-18 require two distinct signals; however, the nature of these signals during inflammation is not completely defined. Studies indicate that the 'first signal' can be triggered by various pathogen-associated molecular patterns following Toll-like receptor (TLR) activation, which induces the synthesis of proIL-1b and proIL-18. The 'second signal' is provided by activation of the inflammasome and casp-1, leading to IL-1b and IL-18 processing.P. aeruginosa reportedly activates IPAF, leading to IL-1b processing 7 . IPAF interacts directly with procaspase-1, which contains the N-terminal caspase recruitment domain 8 . However, maximum casp-1 activation in response to IPAF agonists requires the involvement of apoptosis-associated specklike protein (ASC) 9,10 , a bipartite, caspase recruitment domainand py...

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ATP synthesis and storage

Cited by 370 publications

References 137 publications

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

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

Action of GH on skeletal muscle function: molecular and metabolic mechanisms

Mitochondrial Ca2+-dependent NLRP3 activation exacerbates the Pseudomonas aeruginosa-driven inflammatory response in cystic fibrosis

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