Alcoholic Liver Disease: Update on the Role of Dietary Fat
Abstract
:1. Introduction
2. Dietary Saturated and Unsaturated Fat: Role in ALD Pathogenesis
Animal Models | Dietary Regimen ** | Significant Outcomes | References |
---|---|---|---|
Rats fed EtOH or control liquid diets with a Ritcher drinking tube for eight weeks. | CO + OO + SFO vs. L + SBO; 36%E | Hepatic steatosis and inflammation: CO + OO + SFO + EtOH > L + SBO + EtOH; Hepatic fibrosis: CO + OO + SFO + EtOH < L + SBO + EtOH | [20] |
Rats fed intragastrically EtOH or control liquid diets for four weeks. | MCT vs. CO vs. FO; 25%E | Severity of liver pathology: FO + EtOH > CO + EtOH; MCT + EtOH (no pathological changes) | [15] |
Rats fed intragastrically EtOH or control liquid diets for 10 weeks. | CO (USF diet) vs. BT + MCT (SF diet); 45%E | Liver steatosis, injury, and oxidative stress: USF + EtOH > SF + EtOH. SF protected rats from ALD in a dose-responsive fashion | [6] |
Rats fed solid food and administered EtOH daily (IP) for six weeks | CO vs. CO + OO supplementation (5% wt/wt) | Liver injury, oxidative stress: CO + EtOH > CO + OO + EtOH | [19] |
Rats fed at libitum EtOH or control liquid diets for eight weeks. | CO vs. CB vs. MCT; 30%E | Liver steatosis, macrophage activation, neutrophil infiltration, and hepatic endotoxin levels: CO + EtOH > CB + EtOH or MCT + EtOH; Serum endotoxin levels: CO + EtOH = CB + EtOH; CO + EtOH > MCT + EtOH | [7] |
Mice fed intragastrically EtOH or control liquid diets for three weeks. | CO (USF diet), vs. Hydrogenated soya glyceride (12% palmitic and 85% stearic acids, SF diet); 35%E | Liver steatosis, injury, and oxidative stress: USF + EtOH > SF + EtOH | [8] |
Mice fed at libitum EtOH or control liquid diets for four weeks. | CO vs. CB; 40%E | Liver injury and steatosis: CO + EtOH > CB + EtOH; Plasma adiponectin: CO + EtOH < CB + EtOH | [9] |
Mice fed at libitum EtOH or control liquid diets for eight weeks. | CO (USF diet) vs. BT + MCT (SF diet); 40%E | Liver steatosis, inflammation, and injury: USF + EtOH > SF + EtOH. Intestinal inflammation, alterations in intestinal tight junctions, increased gut permeability and endotoxemia: USF + EtOH > SF + EtOH | [5,21] |
FFAs | Lard | Beef Fat (Tallow) | Cocoa Butter | MCT Oil | Corn Oil | Palm Oil | Fish Oil a | Olive Oil | Safflower Oil | Soybean Oil |
---|---|---|---|---|---|---|---|---|---|---|
Saturated FFAs | ||||||||||
C24:0 | - | - | - | - | - | 0.1 | - | 0.1 | 0.1 | 0.3 |
C22:0 | - | - | 0.2 | - | - | 0.1 | - | 0.1 | 0.3 | 0.2 |
C20:0 | - | 0.1 | 1.2 | - | 0.1 | 0.3 | - | 0.4 | 0.4 | 0.3 |
C19:0 | - | 0.1 | - | - | - | - | - | - | - | |
C18:0 | 14 | 21.6 | 36.4 | - | 2.2 | 4.4 | 2.1 | 2.6 | 2.3 | 3.9 |
C17:0 | - | 1.5 | - | - | 0.1 | - | - | - | - | - |
C16:0 | 26 | 25.5 | 25.1 | - | - | 43.8 | 13.0 | 12.1 | 6.1 | 10.8 |
C15:0 | - | 1.3 | - | - | - | - | - | - | - | - |
C14:0 | 2 | 3.3 | - | - | - | 1.1 | 11.6 | - | - | 0.1 |
C12:0 | - | 0.1 | - | - | - | 0.4 | - | - | - | - |
C10:0 | - | 0.1 | - | 23 (4 > 10:0) | - | 0.1 | - | - | - | - |
C8:0 | - | - | - | 67 (6 < 8:0) | - | 0.1 | - | - | - | - |
Unsaturated FFA (Monounsaturated FFAs) | ||||||||||
C24:1 n9 | - | - | - | - | - | - | - | - | 0.2 | - |
C20:1 n9 | 1 | - | - | - | - | 0.1 | - | 0.3 | 0.2 | 0.1 |
C18:1 n9 | 44 | 38.7 | 34.1 | - | 27.5 | 39.1 | 6.7 | 72.5 | 13.4 | 23.9 |
C18:1 n7 | - | - | - | - | - | - | 3.3 | - | - | - |
C17:1 | - | 0.7 | - | - | - | - | - | 0.2 | - | - |
C16:1 | 3 | 3.4 | - | - | 12.2 | 0.2 | 13.3 | 0.8 | 0.1 | 0.2 |
C15:1 | - | 0.2 | - | - | - | - | - | - | - | |
C14:1 | - | 0.2 | - | - | - | - | - | - | - | - |
Unsaturated FFAs (Polyunsaturated FFAs) | ||||||||||
C22:6 n3 | - | - | - | - | - | - | 8.2 | - | - | - |
C22:5 n6 | - | - | - | - | - | - | 0.4 | - | - | - |
C22:5 n3 | - | - | - | - | - | - | 2.0 | - | - | - |
C20:5 n3 | - | - | - | - | - | - | 17.3 | - | 0.5 | - |
C20:4 n3 | 1.9 | |||||||||
C20:4 n6 | - | 0.4 | - | - | - | - | 0.7 | - | 0.5 | - |
C18:3 n3 | - | 0.6 | 0.2 | - | 0.9 | 0.3 | - | 0.6 | 0.3 | 7.8 |
C18:2 n6 | 10 | 2.2 | 2.8 | - | 57.0 | 10.2 | 1.1 | 9.4 | 76 | 52.1 |
References | [22] | [6] | [23] | [6] | [6] | [23] | [15] | [23] | [23] | [23] |
3. Dietary PUFAs and ALD: The Bad, the Good, and the Controversy
Fatty Acids | Food Sources | Dietary Intake |
---|---|---|
ω3 PUFAs | ||
α-Linolenic Acid, 18:3 ω-3 | Vegetable oils (e.g., soybean and canola). Nuts, and seeds. | 1.4 g/d |
Eicosapentanoic acid, 20:5 ω-3 | Fish (e.g., halibut, mackerel, herring, and salmon) and fish oils | 0.1–0.2 g/d |
Docosahexaenoic acid, 22:6 ω-3 | ||
ω6 PUFAs | ||
Linoleic Acid, 18:2 ω-6 | Vegetable oils (e.g., sunflower, safflower, soybean, corn, and canola), nuts, seeds meats, and eggs | 12–17 g/d |
4. Oxidized Dietary Fat: Relevance to Liver Pathology
5. Oxidized Linoleic Acid Metabolites: Implication for ALD
6. Dietary Fat and EtOH-mediated Changes in the Gut Microbiota
7. Therapeutic Implications of Dietary Lipids in ALD
8. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
AA | arachidonic acid |
AEA | N-arachidonoylethanolamine (anandamide) |
2-AG | 2-arachidonoylglycerol |
ALA | alpha linolenic acid |
ALD | alcoholic liver disease |
ALT | alanine aminotransferase |
AMPK | AMP-activated protein kinase |
CYP2E1 | cytochrome P450 2E1 |
DHA | docosahexaenoic acid |
HNF4α | hepatocyte nuclear factor-4α |
HO-1 | heme oxygenase-1 |
HpODE | hydroperoxy-octadecadienoic acid |
9- and 13-HODEs | 9- and 13-hydroxy-octadecadienoic acids |
EPA | eicosapentaenoic acid |
EtOH | ethanol |
IL-6 | interleukin 6 |
LA | linoleic acid |
LPS | lipopolysaccharide |
12/15-LOX | 12/15-lipoxygenase |
LCFA | long chain fatty acids |
LXA4 | lipoxin A4 |
LXB4 | lipoxin B4 |
MCT | medium chain triglyceride |
NAFLD | nonalcoholic fatty liver disease |
NF-kappaB | nuclear factor kappaB |
OXLAMs | oxidized linoleic acid metabolites |
oxoODE | oxo-octadecadienoic acid |
PPARα | peroxisome proliferator-activated receptor alpha |
PGC-1α | peroxisome proliferator-activated receptor gamma, coactivator 1 alpha |
PUFA | polyunsaturated fatty acid |
ROS | reactive oxygen species |
SF | saturated fat |
SCD-1 | stearoyl-CoA desaturase-1 |
SIRT1 | Sirtuin |
SREBP-1 | sterol regulatory element binding protein-1c |
TJs | tight junctions |
TG | triacylglycerol |
TLR | Toll-like receptors |
TRPV1 | Transient Receptor Potential Vanilloid 1 |
TNF-α | tumor necrosis factor α |
USF | unsaturated fat |
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Kirpich, I.A.; Miller, M.E.; Cave, M.C.; Joshi-Barve, S.; McClain, C.J. Alcoholic Liver Disease: Update on the Role of Dietary Fat. Biomolecules 2016, 6, 1. https://doi.org/10.3390/biom6010001
Kirpich IA, Miller ME, Cave MC, Joshi-Barve S, McClain CJ. Alcoholic Liver Disease: Update on the Role of Dietary Fat. Biomolecules. 2016; 6(1):1. https://doi.org/10.3390/biom6010001
Chicago/Turabian StyleKirpich, Irina A., Matthew E. Miller, Matthew C. Cave, Swati Joshi-Barve, and Craig J. McClain. 2016. "Alcoholic Liver Disease: Update on the Role of Dietary Fat" Biomolecules 6, no. 1: 1. https://doi.org/10.3390/biom6010001