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250 YurgilK.BarkauskasD.VasterlingJ.NievergeltC.LarsonG.SchorkN.et al (2014)

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Other approaches include humanised bispecific or monoclonal antibodies activating the FGFR1/-Klotho complex and have been shown to improved liver fat content and serum lipids.175 Thyroid hormone receptor Thyroid hormones stimulate hepatic fatty acid oxidation as well as cholesterol and phospholipid excretion into bile.179 180 THR include different isoforms and in liver THR-1 isoform represents 80% of THRs, while 20% are represented by THR-1.181 Selective modulation of THR-1 allows targeting hepatic genes without cardiac side effects.181 182 Numerous studies have linked subclinical hypothyroidism and low thyroid function with NAFLD, NASH and fibrosis as well as cardiovascular mortality.182 183 Low-dose thyroid hormone treatment reduced hepatic lipid content in patients with diabetes with NAFLD184 Two promising thyromimetic compounds specifically targeting THR-1 in the liver, resmetirom (MGL-3196) and VK2809 are currently studied and have shown already beneficial effects in phase 2 studies in NASH with additional beneficial impact on associated cardiometabolic risk profiles (table 1).185 PBC is frequently associated with other autoimmune diseases including Hashimotos thyroiditis and hypothyroidism may aggravate cholestasis in PBC186 187 since thyroid hormones and THR-1 regulate BA homoeostasis and bile formation180 188 including stimulation of biliary phospholipid excretion via ABCB4.188 Notably, defective ABCB4 expression and function results in bile duct injury and various cholestatic syndromes39 emphasising its relevance as therapeutic target

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Cai PY, Bodhit A, Derequito R, Ansari S, Abukhalil F, Thenkabail S, Ganji S, Saravanapavan P, Shekar CC, Bidari S, Waters MF, Hedna VS (2014) Vagus nerve stimulation in ischemic stroke: old wine in a new bottle