\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Chronic amiodarone administration causes liver damage via adipose tissue
ER-stress dependent lipolysis, leading to hepatotoxic free fatty acid
accumulation}



\author[1]{Einav Hubel}%
\author[1]{Sigal Fishman}%
\author[2]{Minna Holopainen}%
\author[2]{Reijo Kakela}%
\author[1]{Ortal Shaffer}%
\author[1]{Inbal Houri}%
\author[1]{Roy Avraham}%
\author[1]{Isabel Zvibel}%
\author[1]{Oren Shibolet}%
\affil[1]{Tel Aviv Sourasky Medical Center}%
\affil[2]{University of Helsinki}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background and Purpose: Drug induced liver injury is an emerging form of
acute and chronic liver disease that may manifest as fatty liver.
Amiodarone (AMD), a widely used anti-arrhythmic drug, can cause hepatic
injury and steatosis by a variety of mechanisms, which are not
completely understood. Experimental Approach: Chronic damage was induced
by daily gavage of 180mg/kg body weight AMD for four consecutive days to
C57Bl/6OlaHsd male mice. Key Results: Chronic AMD administration induced
endoplasmic reticulum (ER) stress in both liver and adipose tissue. In
adipose tissue, AMD reduced lipogenesis and increased lipolysis.
Moreover, AMD treatment induced ER stress and ER stress-dependent
lipolysis in 3T3L1 adipocytes in vitro. In the liver, AMD caused
increased expression of genes encoding proteins involved in fatty acid
(FA) uptake and transfer (Cd36, Fabp1 and Fabp4) and resulted in
increased hepatic accumulation of free FAs, but not of triacylglycerols.
In line with this, there was increased expression of hepatic de novo FA
synthesis genes (Srebp1 and FA synthase encoded by Fasn). However, AMD
significantly reduced the expression of the desaturase Scd1 and elongase
Elovl6, detected at mRNA and protein levels. Accordingly, the FA profile
of hepatic total lipids revealed increased accumulation of palmitate, a
SCD1 and ELOVL6 substrate, and reduced levels of palmitoleate and
cis-vaccenate, products of the enzymes. In addition, AMD-treated mice
displayed increased hepatic apoptosis, known to be induced by lipotoxic
palmitate. Conclusions and Implications: Chronic AMD induced ER stress
and aggravated lipolysis in adipose tissue, while inducing a lipotoxic
hepatic lipid environment.%
\end{abstract}%



\sloppy


\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5/Figure-5}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-6/Figure-6}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

