Abstract
Angiopoietin-like protein 8 (Angptl8), a recently identified member of the angiopoietin-like protein family (ANGPTLs), is a 22-kDa peptide synthesized in the liver. It participates in lipid metabolism by inhibiting lipoprotein lipase (LPL) activity, consequently increasing the triglyceride levels. Despite evidence that Angptl8 is involved in feeding control, the underlying mechanisms are unclear. Central and peripheral injections of Angptl8 significantly decreased food intake. Angptl8 was widely expressed in appetite-related nuclei, including the paraventricular nucleus (PVN), the dorsomedial hypothalamus (DMH), the ventromedial hypothalamus, and the arcuate nucleus (ARC) in the hypothalamus. Peripheral Angptl8 administration decreased c-Fos-positive neurons in the DMH. Central Angptl8 administration decreased c-Fos-positive neurons in the DMH and PVN but increased these neurons in the ARC. Angptl8 inhibited appetite via neuropeptide Y (NPY) neurons in the DMH. Furthermore, the chronic administration of Angptl8 decreased body weight gain and altered adipose tissue deposits. Nevertheless, neither peripheral nor central Angptl8 influenced the brown adipose tissue (BAT) morphology or uncoupling protein 1 (Ucp-1) expression in BAT. Taken together, these data suggested that Angptl8 modulates appetite and energy homeostasis.
Highlights
Angiopoietin-like protein 8 (Angptl8) is a 22-kDa peptide synthesized in the liver (Ren et al, 2012)
Angptl8 induced a concentration-dependent decrease in food intake beginning at 2 h and this decrease was sustained for 12 h after the injection
We found that, compared with normal saline (NS)-treated counterparts, I.C.V. microinjections of Angptl8 (0.3 μg/μl) significantly reduced nocturnal cumulative food intake beginning at 2 h (0.65 ± 0.08 vs. 1.14 ± 0.09 g, P < 0.05; Figure 1B), which was sustained until 6 h (2.00 ± 0.28 vs. 3.82 ± 0.25 g, P < 0.05; Figure 1B)
Summary
Angiopoietin-like protein 8 (Angptl8) is a 22-kDa peptide synthesized in the liver (Ren et al, 2012). The receptor of Angptl has not been discovered, it is widely distributed in white adipose tissue (WAT), BAT, and the brain (Quagliarini et al, 2012). Fasting suppresses Angptl expression in Abbreviations: Angptl, angiopoietin-like protein 8; ARC, arcuate nucleus; BAT, brown adipose tissue; DMH, dorsomedial hypothalamus; FFA, free fatty acid; LPL, lipoprotein lipase; NPY, neuropeptide Y; PVN, paraventricular nucleus; Ucp-1, uncoupling protein 1; VMH, ventromedial hypothalamus. Angptl Inhibited Appetite via NPY the liver, while refeeding increases its expression levels (Quagliarini et al, 2012; Zhang and Abou-Samra, 2013), suggesting that circulating Angptl is involved in the feeding control. As Angptl is distributed in both peripheral tissues and the brain (Quagliarini et al, 2012), we hypothesized that Angptl has different effects on energy homeostasis in the peripheral and central systems, like Angptl (Kim et al, 2015); the effects of peripheral and central administration were both examined
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