Figure 1 Thyroid hormone effects on hepatic lipid metabolism

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Presentation transcript:

Figure 1 Thyroid hormone effects on hepatic lipid metabolism Figure 1 | Thyroid hormone effects on hepatic lipid metabolism. Thyroid hormone stimulates lipolysis from fat stores in white adipose tissue and from dietary fat sources (high-fat diets) to generate free fatty acids (FFAs) that enter the hepatic cells via protein transporters such as fatty acid transporter protein (FATP), liver fatty acid binding protein (L‑FABP) and CD36. Thyroid hormone induces de novo lipogenesis (DNL) via the transcription of several key lipogenic genes such as Acc1, Fasn, Me and Thrsp. In addition, thyroid hormone indirectly controls the transcriptional regulation of hepatic DNL by regulating the expression and activities of other transcription factors such as sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP). DNL is also driven by the influx of high levels of carbohydrate or glucose derived from high-carbohydrate diets via glucose transporters (GLUTs), which are shuttled to FFA generation. FFAs are typically esterified to triacylglycerol and subsequently packaged into VLDL for export or stored as intracellular lipid droplets. Triacylglycerol stored as lipid droplets can also be hydrolysed back to FFAs via classic lipases and lipophagy (by regulating transcription factor EB (TFEB), NAD-dependent protein deacetylase sirtuin 1 (SIRT1) and forkhead box protein O1 (FOXO1)), undergo mitochondrial β‑oxidation by the activity of various co‑activators or nuclear receptors (such as peroxisome proliferator-activated receptor-α (PPARα), oestrogen-related receptor-α (ERRα), fibroblast growth factor 21 (FGF21) and PPARγ co-activator 1α (PGC1α)) and target the transcription of genes such as Cpt1a, Mcad (also known as Acadm), Pdk4 and Ucp2. ↑/↓ depicts the positive or negative effect that thyroid hormone action has on the cellular process shown, respectively. OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species; TCA, tricarboxylic acid. Sinha, R. A. et al. (2018) Direct effects of thyroid hormones on hepatic lipid metabolism Nat. Rev. Endocrinol. doi:10.1038/nrendo.2018.10