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synergy · 1
Many drugs are first processed in the liver and then excreted through the kidneys. Damage to either the liver or the kidney adds to the load on the other, and drugs are more likely to build up in the body. Older adults taking several medicines at once face this risk most.
cofactor · 1
Glutathione neutralizes peroxides only with the help of glutathione peroxidase (GPx), an enzyme whose active site is a selenium-containing amino acid, selenocysteine. So this antioxidant defense in the liver depends on selenium.
regulates · 8
The liver secretes bile every day to help the gut digest fat; most bile acids are reabsorbed at the end of the small intestine and, through receptors such as FXR, send signals back to the liver that regulate bile-acid and fat metabolism. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly called non-alcoholic fatty liver disease), this gut-liver loop can be disturbed and is thought to be one factor that makes the disease worse.
The liver is the hub of blood lipids: it packs fat into very-low-density lipoprotein (VLDL) and sends it into the blood, so fatty liver often comes with abnormal blood lipids. In people with fatty liver, cardiovascular disease often causes trouble before the liver does: fatty liver is not just a liver problem.
Taylor's twin-cycle hypothesis holds that when the liver carries too much fat (more than 5% counts as fatty liver), it exports more fat into the blood, the fat settles in the pancreas, the insulin-making beta cells decline, and type 2 diabetes follows; losing enough weight may run the chain in reverse. In DiRECT, the more weight people lost, the more of them went into remission, which fits the hypothesis.
Venous blood from the gut flows straight into the liver through the portal vein, so the products of gut bacteria (endotoxin, short-chain fatty acids, secondary bile acids) are important signals for liver metabolism and inflammation. One explanation holds that once fat has built up in the liver, further hits such as endotoxin from the gut may push fatty liver on to metabolic dysfunction-associated steatohepatitis (MASH).
Long-term drinking increases a liver enzyme called CYP2E1. The reactive oxygen species it produces keep damaging the liver, and it converts more acetaminophen (a common fever and pain reliever) into a toxic metabolite. There are case reports of acute liver failure in heavy long-term drinkers who took this drug at ordinary doses.
The liver plays several endocrine roles: it converts thyroxine (T4) into the more active T3, makes most of the body's IGF-1 on orders from growth hormone, and is one of the main organs insulin acts on. So obesity, fatty liver and hormone disturbances are often several sides of the same metabolic problem.
The liver hosts Kupffer cells, the largest population of resident macrophages in the body. In metabolic dysfunction-associated steatohepatitis (MASH), bacterial endotoxin arriving from the gut can activate them and inflame the liver; the liver also makes acute-phase proteins such as C-reactive protein, which take part in inflammation throughout the body.
The thousands of plant chemicals in food that no nutrition label lists are mostly processed in the body by cytochrome P450 (CYP) enzymes in the liver and gut wall, a system that exists to handle foreign molecules (Guengerich 2008). One visible consequence is that food and drugs affect each other: furanocoumarins in grapefruit inhibit CYP3A4 in the gut, so some drugs cleared by that enzyme reach higher levels in the blood (Bailey 2013). People taking such drugs should ask a doctor or pharmacist before eating grapefruit.
contrast · 1
Milk thistle is the most common ingredient in liver-support pills, but the liver's two-step process for clearing foreign substances (phase I and phase II metabolism) runs all the time anyway; pooled randomized trials found no effect of milk thistle on death or complications in people with liver disease.