NAFLD, Estrogens, and Physical Exercise: The Animal Model

Table 1

Summary of the central and intrahepatic effects resulting in liver fat accumulation with estrogens withdrawal.

Central effects	Intra-hepatic effects
CNS/hypothalamic effects	Lipid uptake
(i) ↑ Food consumption; (ii)↑ Leptin secretion; (iii) ↓ Activity and energy expenditure	(i) Unknown (possible mechanism of upregulation of fatty acid uptake via estrogens-dependent pathways, yet to be explored)
Lipid profile and adipose tissue effects	Lipogenesis
(i) Absence of estrogens causes fat redistribution/gain particularly increased intra-abdominal fat and altered lipid homeostasis (portal/fatty acid flux theory)	(i) ↑ SREBP-1c and PGC1α; (ii) ↑ SCD-1; (iii) ↑ FAS; (iv) ↑ ACC; (v) ↑ PPAR-γ
	Lipid oxidation
	(i) ↓ PPAR-α; (ii) ↓ HSL; (iii) ↓ Fatty acid β-oxidation
	VLDL-TG production and secretion system
	(i) ↓ VLDL-TG production in Ovx rats; (ii) ↓ MTP and DGAT2

CNS: central nervous system; SREBP-1c: sterol-regulatory-element-binding-protein 1c; PGC1α: peroxisome proliferator-activated receptor gamma coactivator-1 alpha; SCD-1: stearoyl-CoA desaturase-1; FAS: fatty acid synthase; ACC: acetyl-CoA carboxylase; PPAR-α, -γ: peroxysome proliferator-activated receptor-alpha, -gamma; HSL: hormone-sensitive lipase; VLDL-TG: very low density lipoprotein-triglyceride; MTP: microsomal triglyceride transfer protein; DGAT2: diacyl-glycerol acyltransferase-2.