Lipid metabolism in chronic obstructive pulmonary disease

Figures & data

Figure 1 Metabolic pathway of glycolysis, FAS and FAO. Glycolysis converts glucose into pyruvate, which can enter the tricarboxylic acid (TCA) cycle. Glycolysis also feeds the pentose phosphate pathway (PPP), which generates ribose for nucleotides and NADPH. Citrate can be fully oxidized to generate ATP or transported to the cytoplasm where it is converted back to acetyl-CoA by ATP citrate lyase (ACLY). A portion of the acetyl-CoA is carboxylated to malonyl-CoA by acetyl-CoA carboxylase 1 (ACC1). Fatty acid synthase (FAS) performs the condensation of acetyl-CoA and malonyl-CoA to produce the 16-carbon saturated fatty acid palmitate and other saturated long-chain FAs. In the cytosol, fatty acy-CoA synthases (ACS) activate fatty acids by converting them to fatty acyl-CoA. Fatty acyl-CoA is converted to acylcarnitine by CPT1 on ther outer mitochondrial membrane and transported to the mitochondrial matrix. In the mitochondrial matrix, fatty acyl-CoA is oxidized to acetyl-CoA through fatty acid oxidation.

Abbreviations: ACC1, acetyl-CoA carboxylase α; ACLY, ATP citrate lyase; ACS, acyl-CoA synthase; CPT1, carnitine palmitoyltransferase 1; FAS, fatty acid synthase; TCA cycle, tricarboxylic acid cycle.

Table 1 Lipids alterations in COPD

Lipids metabolic events	Targets	Major outcome(s)	References
Fatty acid oxidation pathway	Alveolar type 2 cells	Oxidative metabolism was activated after subchronic cigarette smoke exposure. Enhancement of FAO affected the surfactant biosynthesis pathway in lung type 2 cells.	^Citation21, ^Citation28
	Bronchial epithelial cells	Cigarette smoke exposure promoted fatty acid oxidation, and sustained elevation in FAO may aggravate ROS accumulation, mitochondrial damage, and cell death.	^Citation29
	Airway smooth muscle cell	Fatty acid oxidation capacity was reduced under unstimulated conditions.	^Citation33
Catabolic lipid mediators
Prostanoids	Fibroblasts	Increased PGE2 contributed to airway inflammation and the impaired lung repair.	^Citation38–Citation40
Leukotrienes	Sputum	LTB4 increased in induced sputum.	^Citation42, ^Citation43
Resolvins	Lung tissue	D-series resolvins altered in human lung samples of COPD. Treatment of resolving D1 decreased inflammatory cytokines and enhanced phagocytosis of macrophages.	^Citation45–Citation47
Nitrated fatty acids	Macrophages	NFA treatment downregulated production of inflammatory cytokines and chemokines in macrophages.	^Citation48
Fatty acid synthesispathway	Bronchial epithelial cells	Long-term cigarette smoke exposure might lead to increased glucose consumption and enhanced lipid biosynthesis.	^Citation55, ^Citation56
Transcription factors
PPAR-γ	Lung tissue, epithelial cells, and myeloid cells	PPAR-γ was downregulated in those targets, which increased susceptibility to chronic CS-induced emphysema and expression of chemokines.	^Citation62–Citation64
LXR	Lung tissue	LXR increased in lung tissue, located in small airway and alveolar epitheliums.	^Citation67
Cholesterol or oxidized cholesterol	Serum, bronchial epithelial cells	The level of cholesterol was higher in serum of patients with very severe COPD. Oxidized cholesterol products were elevated in the airway of COPD patients. Hydroxycholesterol contributed to the inflammation and CS-induced emphysema.	^Citation73–Citation78
Phospholipids	Sputum, Plasma, lung tissue	Sphingolipids was higher in COPD patients in sputum. Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes. Upregulation of ceramide in lung tissue implicated in alveolar cell apoptosis.	^Citation84, ^Citation85, ^Citation87

Abbreviations: COPD, chronic obstructive pulmonary disease; CS, cigarette smoke; FAO, fatty acid oxidation; FAS, fatty acid synthesis; LXR, liver X receptor; LTB₄, leukotriene B4; PGE₂, prostaglandin E2; PPAR-γ, peroxisome proliferator activated receptors-γ; ROS, reactive oxygen species.

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