Kinetic proteomics identifies targeted changes in liver metabolism and the ribo-interactome by dietary sulfur amino acid restriction

Fuente: Zenodo

Guardado en:

Detalles Bibliográficos
Autores principales:	Jonsson, William, Borowik, Agnieszka, Pranay, Atul, Kinter, Michael, Mirek, Emily, Levy, Jordan, Snyder, Elizabeth, Miller, Benjamin, Anthony, Tracy
Formato:	Recurso digital
Lenguaje:	inglés
Publicado:	Zenodo 2022
Materias:	healthspan protein synthesis transcripomics high-fat diet mice proteomics
Acceso en línea:	Acceder al recurso
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

_version_	1866901305490931712
author	Jonsson, William Borowik, Agnieszka Pranay, Atul Kinter, Michael Mirek, Emily Levy, Jordan Snyder, Elizabeth Miller, Benjamin Anthony, Tracy
author_facet	Jonsson, William Borowik, Agnieszka Pranay, Atul Kinter, Michael Mirek, Emily Levy, Jordan Snyder, Elizabeth Miller, Benjamin Anthony, Tracy
contents	<p>Dietary sulfur amino acid (SAA) restriction (SAAR) protects against diet-induced obesity, extends healthspan and coincides with an overall reduction in hepatic protein synthesis. To explore the underpinnings of SAAR-induced slowed growth and its benefits on proteostasis control, we resolved changes in hepatic mRNA and protein abundances and compared synthesis rates of 820 individual liver proteins. To achieve this, adult male mice were provided deuterium-labeled drinking water while freely consuming either a regular-fat or high fat diet that was restricted in SAA. Livers from these mice and their respective dietary controls were used to conduct transcriptomic, proteomic, and kinetic proteomic analyses. We found that remodeling of the transcriptome by SAAR was largely agnostic to dietary fat content. Shared signatures included activation of the integrated stress response alongside alterations in metabolic processes impacting lipids, fatty acids, and amino acids. Changes to the proteome correlated poorly with the transcriptome and yet, functional clustering of kinetic proteomic changes in liver during SAAR revealed that management of fatty acids and amino acids were altered to support central metabolism and redox balance. Dietary SAAR also strongly influenced the synthesis rates of ribosomal proteins and ribosome-interacting proteins regardless of dietary fat. Taken together, dietary SAAR alters the transcriptome and kinetic proteome in liver to safely manage increased fatty acid flux and energy use, and couples this with targeted changes in the ribo-interactome to support proteostasis and slowed growth.</p>
format	Recurso digital
id	zenodo_https___doi_org_10_5281_zenodo_7215980
institution	Zenodo
language	eng
publishDate	2022
publisher	Zenodo
record_format	zenodo
spellingShingle	Kinetic proteomics identifies targeted changes in liver metabolism and the ribo-interactome by dietary sulfur amino acid restriction Jonsson, William Borowik, Agnieszka Pranay, Atul Kinter, Michael Mirek, Emily Levy, Jordan Snyder, Elizabeth Miller, Benjamin Anthony, Tracy healthspan protein synthesis transcripomics high-fat diet mice proteomics <p>Dietary sulfur amino acid (SAA) restriction (SAAR) protects against diet-induced obesity, extends healthspan and coincides with an overall reduction in hepatic protein synthesis. To explore the underpinnings of SAAR-induced slowed growth and its benefits on proteostasis control, we resolved changes in hepatic mRNA and protein abundances and compared synthesis rates of 820 individual liver proteins. To achieve this, adult male mice were provided deuterium-labeled drinking water while freely consuming either a regular-fat or high fat diet that was restricted in SAA. Livers from these mice and their respective dietary controls were used to conduct transcriptomic, proteomic, and kinetic proteomic analyses. We found that remodeling of the transcriptome by SAAR was largely agnostic to dietary fat content. Shared signatures included activation of the integrated stress response alongside alterations in metabolic processes impacting lipids, fatty acids, and amino acids. Changes to the proteome correlated poorly with the transcriptome and yet, functional clustering of kinetic proteomic changes in liver during SAAR revealed that management of fatty acids and amino acids were altered to support central metabolism and redox balance. Dietary SAAR also strongly influenced the synthesis rates of ribosomal proteins and ribosome-interacting proteins regardless of dietary fat. Taken together, dietary SAAR alters the transcriptome and kinetic proteome in liver to safely manage increased fatty acid flux and energy use, and couples this with targeted changes in the ribo-interactome to support proteostasis and slowed growth.</p>
title	Kinetic proteomics identifies targeted changes in liver metabolism and the ribo-interactome by dietary sulfur amino acid restriction
topic	healthspan protein synthesis transcripomics high-fat diet mice proteomics
url	https://doi.org/10.5281/zenodo.7215980

if (filemtime($filename) + $maxlifetime < time()) { unlink($filename); $count++; } } return $count; } /** * A function that is called internally when session data is to be saved. * * @param string $sessId The current session ID * @param string $data The session data to write * * @return bool */ protected function saveSession($sessId, $data): bool { $sessFile = $this->path . '/sess_' . $sessId; if ($handle = fopen($sessFile, 'w')) { $return = false; // Lock the file for exclusive access to avoid issues with multiple // processes writing session simultaneously: if (flock($handle, LOCK_EX)) { $return = fwrite($handle, $data); // Make sure that there's no trailing data by truncating the file to // the correct length: ftruncate($handle, strlen($data)); fflush($handle); flock($handle, LOCK_UN); } fclose($handle); if ($return !== false) { return true; } } // If we got this far, something went wrong with the file output... // It is tempting to throw an exception here, but this code is called // outside of the context of exception handling, so all we can do is // echo a message.

// Anecdotal testing Today and Yesterday seems to indicate destroy() // is called by the garbage collector and everything is good. // Something to keep in mind though. return 0; } /** * Write function that is called when session data is to be saved. * * @param string $sessId The current session ID * @param string $data The session data to write * * @return bool */ public function write($sessId, $data): bool { if ($this->writesDisabled) { return true; } return $this->saveSession($sessId, $data); } /** * A function that is called internally when session data is to be saved. * * @param string $sessId The current session ID * @param string $data The session data to write * * @return bool */ abstract protected function saveSession($sessId, $data): bool; }

* * @return void */ public function writeClose() { // The assumption is that we're using PHP's ext/session. // session_write_close() will actually overwrite $_SESSION with an // empty array on completion -- which leads to a mismatch between what // is in the storage object and $_SESSION. To get around this, we // temporarily reset $_SESSION to an array, and then re-link it to // the storage object. // // Additionally, while you _can_ write to $_SESSION following a // session_write_close() operation, no changes made to it will be // flushed to the session handler. As such, we now mark the storage // object isImmutable. $storage = $this->getStorage(); if (! $storage->isImmutable()) { $_SESSION = $storage->toArray(true); session_write_close(); $storage->fromArray($_SESSION); $storage->markImmutable(); } } /** * Attempt to set the session name * * If the session has already been started, or if the name provided fails * validation, an exception will be raised. * * @param string $name * @return SessionManager * @throws Exception\InvalidArgumentException */ public function setName($name) { if ($this->sessionExists()) { throw new Exception\InvalidArgumentException( 'Cannot set session name after a session has already started'

Environment & details:

GET Data empty

POST Data empty

Files empty

Key	Value
ui	"standard"
language	"es"
VUFIND_SESSION	"9c1e0c97d0f631cf5dc7a3a616d08e7c"

Session

Key	Value
__Laminas	array:2 [`"_REQUEST_ACCESS_TIME" => 1788922911.1346 "_VALID" => array:1 [ "Laminas\Session\Validator\Id" => "9c1e0c97d0f631cf5dc7a3a616d08e7c" ]`]
SessionState	Laminas\Stdlib\ArrayObject {#938}
FlashMessenger	Laminas\Stdlib\ArrayObject {#1455}
SessionHelper	Laminas\Stdlib\ArrayObject {#1785}

Server/Request Data

Key	Value
REDIRECT_VUFIND_LOCAL_DIR	"/usr/local/vufind/local"
REDIRECT_HTTPS	"on"
REDIRECT_SSL_TLS_SNI	"info.umar.mx"
REDIRECT_STATUS	"200"
VUFIND_LOCAL_DIR	"/usr/local/vufind/local"
HTTPS	"on"
SSL_TLS_SNI	"info.umar.mx"
HTTP_ACCEPT	"/"
HTTP_USER_AGENT	"Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)"
HTTP_COOKIE	"ui=standard; language=es; VUFIND_SESSION=9c1e0c97d0f631cf5dc7a3a616d08e7c"
HTTP_ACCEPT_ENCODING	"gzip, br, zstd, deflate"
HTTP_HOST	"info.umar.mx"
PATH	"/usr/local/sbin:/usr/local/bin:/usr/sbin:/usr/bin:/snap/bin"
SERVER_SIGNATURE	"<address>Apache/2.4.66 (Ubuntu) Server at info.umar.mx Port 443</address>\n"
SERVER_SOFTWARE	"Apache/2.4.66 (Ubuntu)"
SERVER_NAME	"info.umar.mx"
SERVER_ADDR	"200.23.222.19"
SERVER_PORT	"443"
REMOTE_ADDR	"216.73.217.2"
DOCUMENT_ROOT	"/usr/local/vufind/public"
REQUEST_SCHEME	"https"
CONTEXT_PREFIX	""
CONTEXT_DOCUMENT_ROOT	"/usr/local/vufind/public"
SERVER_ADMIN	"admin@localhost"
SCRIPT_FILENAME	"/usr/local/vufind/public/index.php"
REMOTE_PORT	"32819"
REDIRECT_URL	"/Record/zenodo_https___doi_org_10_5281_zenodo_7215980/Details"
GATEWAY_INTERFACE	"CGI/1.1"
SERVER_PROTOCOL	"HTTP/1.1"
REQUEST_METHOD	"GET"
QUERY_STRING	""
REQUEST_URI	"/Record/zenodo_https___doi_org_10_5281_zenodo_7215980/Details"
SCRIPT_NAME	"/index.php"
PHP_SELF	"/index.php"
REQUEST_TIME_FLOAT	1788922911.1297
REQUEST_TIME	1788922911

Environment Variables empty

Registered Handlers

0. Whoops\Handler\PrettyPageHandler

Environment & details:

GET Data empty

POST Data empty

Files empty

Key	Value
ui	"standard"
language	"es"
VUFIND_SESSION	"9c1e0c97d0f631cf5dc7a3a616d08e7c"

Session

Key	Value
__Laminas	array:2 [`"_REQUEST_ACCESS_TIME" => 1788922911.1346 "_VALID" => array:1 [ "Laminas\Session\Validator\Id" => "9c1e0c97d0f631cf5dc7a3a616d08e7c" ]`]
SessionState	Laminas\Stdlib\ArrayObject {#938}
FlashMessenger	Laminas\Stdlib\ArrayObject {#1455}
SessionHelper	Laminas\Stdlib\ArrayObject {#1785}

Server/Request Data

Key	Value
REDIRECT_VUFIND_LOCAL_DIR	"/usr/local/vufind/local"
REDIRECT_HTTPS	"on"
REDIRECT_SSL_TLS_SNI	"info.umar.mx"
REDIRECT_STATUS	"200"
VUFIND_LOCAL_DIR	"/usr/local/vufind/local"
HTTPS	"on"
SSL_TLS_SNI	"info.umar.mx"
HTTP_ACCEPT	"/"
HTTP_USER_AGENT	"Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)"
HTTP_COOKIE	"ui=standard; language=es; VUFIND_SESSION=9c1e0c97d0f631cf5dc7a3a616d08e7c"
HTTP_ACCEPT_ENCODING	"gzip, br, zstd, deflate"
HTTP_HOST	"info.umar.mx"
PATH	"/usr/local/sbin:/usr/local/bin:/usr/sbin:/usr/bin:/snap/bin"
SERVER_SIGNATURE	"<address>Apache/2.4.66 (Ubuntu) Server at info.umar.mx Port 443</address>\n"
SERVER_SOFTWARE	"Apache/2.4.66 (Ubuntu)"
SERVER_NAME	"info.umar.mx"
SERVER_ADDR	"200.23.222.19"
SERVER_PORT	"443"
REMOTE_ADDR	"216.73.217.2"
DOCUMENT_ROOT	"/usr/local/vufind/public"
REQUEST_SCHEME	"https"
CONTEXT_PREFIX	""
CONTEXT_DOCUMENT_ROOT	"/usr/local/vufind/public"
SERVER_ADMIN	"admin@localhost"
SCRIPT_FILENAME	"/usr/local/vufind/public/index.php"
REMOTE_PORT	"32819"
REDIRECT_URL	"/Record/zenodo_https___doi_org_10_5281_zenodo_7215980/Details"
GATEWAY_INTERFACE	"CGI/1.1"
SERVER_PROTOCOL	"HTTP/1.1"
REQUEST_METHOD	"GET"
QUERY_STRING	""
REQUEST_URI	"/Record/zenodo_https___doi_org_10_5281_zenodo_7215980/Details"
SCRIPT_NAME	"/index.php"
PHP_SELF	"/index.php"
REQUEST_TIME_FLOAT	1788922911.1297
REQUEST_TIME	1788922911

Environment Variables empty

Registered Handlers

0. Whoops\Handler\PrettyPageHandler

Ejemplares similares

Environment & details:

Environment & details: