Nonalcoholic fatty liver disease (NAFLD) is prevalent clinically and can lead to more serious chronic liver disease. However, the pathological mechanism is still unclear, and thus, there are no approved drugs on the market. Transcriptional coactivator WW domain-binding protein 2 (WBP2) is a newly discovered oncogene that has an important relationship with the occurrence and development of breast cancer and mediates the interaction between Wnt and various other signaling pathways. The expression level of WBP2 was decreased in NAFLD. Overexpression of WBP2 with AAV in vivo alleviated liver fat deposition and insulin resistance induced by a high-fat diet (HFD). Knockdown of WBP2 with AAV aggravated HFD-induced fatty liver and insulin resistance. In vitro experiments showed that in the human normal hepatocyte cell line LO2 and primary hepatocytes isolated from mice, overexpression of WBP2 reduced fat deposition, and knocking out or knocking down WBP2 aggravated PA-induced fat deposition. Through mass spectrometry, we found that WBP2 can bind to AMPKβ1, and by mutating AMPKβ1, we found that WBP2 can induce phosphorylation of AMPKβ1 at S108 and then activate the AMPK pathway to affect lipid metabolism. The effect of WBP2 on NAFLD provides a possible new direction for future research on NAFLD.

Endothelial cells are the fundamental components of blood vessels that regulate several physiological processes including immune responses, angiogenesis, and vascular tone. Endothelial dysfunction contributes to the development of various diseases such as acute lung injury, and endothelial inflammation is a vital part of endothelial dysfunction. Dauricine is an extract isolated from Menispermum dauricum DC, a traditional Chinese medical plant that can be used for pharyngitis. In this work, we found that IL-1β-induced overexpression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin was inhibited by dauricine in primary human umbilical vein endothelial cells (HUVECs). Correspondingly, adhesion of human acute monocytic leukemia cell line (THP-1) to HUVECs was decreased by dauricine. Further studies showed that dauricine inhibited the activation of nuclear factor-κB (NF-κB) pathway in HUVECs stimulated with IL-1β. In vivo, dauricine protected mice from lipopolysaccharide (LPS)-induced acute lung injury. In lung tissues, the activation of NF-κB pathway and the expression of its downstream genes (ICAM-1, VCAM-1, and E-selectin) were decreased by dauricine, consistent with what was found in vitro. In summary, we concluded that dauricine could alleviate endothelial inflammation by suppressing NF-κB pathway, which might serve as an effective candidate for diseases related with endothelial inflammation.

Diet‐induced obesity (DIO) is associated with several adverse metabolic changes including development of insulin resistance. Aerobic exercise (EX) &/or caloric restriction (CR) can improve many metabolic abnormalities. To examine independent & combined effects of EX & CR on global metabolism after DIO, male Wistar rats were fed a high fat diet (HF, 45%) ad‐libitum for 12 wk, then divided into 4 groups: continued HF diet (HF), 20% CR of HF (CR), ~20% caloric expenditure via EX (EX), or 10% CR + ~10% expenditure via EX (CR+EX). Controls were fed a low fat diet (LF) & samples were collected at 2 & 8 wk. Body weights in CR, EX & CR+EX were lower than LF or HF. Insulin sensitivity was impaired in HF compared to other groups. Preliminary metabolomics analyses show elevated plasma amino acids including leucine/isoleucine, methionine, phenylalanine & tyrosine, & acylcarnitine (AC) species C18:1 & C18:2 at 2 vs 8 wk in EX only. CR, EX or CR+EX often normalized liver AC toward LF values (e.g. C3, C16). DIO rats had lower respiratory exchange ratios (RER) & heat production vs LF, but values were higher in EX & CR+EX vs HF or CR. We conclude CR & EX induce similar improvement in insulin sensitivity but interventions including exercise result in additional changes in the metabolic profile compared to CR alone.Supported by NIH grant PO1‐DK58398 and a grant from the Duke‐NUS, Singapore. E. Glynn was supported by the Jeane B. Kempner Scholar Award Fund.