Dataset Information

MS-based quantitative proteomic analysis of MAM from WT and obese mice.

ABSTRACT: Diabetic cardiomyopathy (DCM) strongly leads to heart failure, notably with preserved ejection fraction (HFpEF). The involvement of mitochondria-associated reticular membranes (MAM) in T2D-related metabolic disorders starts to be demonstrated. In order to characterize the cardiac phenotype of an obesogenic type II diabetic mouse model (leptin-deficient ob/ob), we compared the proteome of its MAMs with those from WT mice.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Yohann Couté

LAB HEAD: Yohann Couté

PROVIDER: PXD054672 | Pride | 2025-06-16

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 18

Publications

Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the <i>ob/ob</i> mouse model.

Guedouari Hala H Dia Maya M Geoffray Juliette J Brun Camille C Moulin Florentin F Givre Lucas L Belmudes Lucid L Leon Christelle C Chanon Stephanie S Ji-Cao Jingwei J Chouabe Christophe C Ducreux Sylvie S Crola Da Silva Claire C Gomez Ludovic L Couté Yohann Y Thibault Helene H Rieusset Jennifer J Paillard Melanie M

Journal of molecular and cellular cardiology plus 20250510

Type 2 diabetes (T2D) and obesity strongly lead to diabetic cardiomyopathy (DCM). The involvement of mitochondria-associated reticular membranes (MAMs), a signaling hub in the cardiomyocyte, starts to be demonstrated in T2D-related metabolic disorders. We recently discovered a cardiac MAM Ca<sup>2+</sup> uncoupling in a high-fat high-sucrose diet (HFHSD)-induced mouse model of DCM. To better determine the role of MAMs in the progression of DCM, we here aimed to characterize the proteomic composi ...[more]

PMID: 40492240

Similar Datasets

Project description:Caloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling Growing evidence supports an anti-lipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin deficient ob/ob mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction in leptin deficiency. Echocardiography was performed on C57Bl/6 wild-type mice (WT) and 7-month-old ob/ob mice fed ad lib, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for four weeks. Ventricular tissue was examined by electron microscopy (EM), mitochondrial coupling assay, and microarray expression profiling. LR and CR-ob/ob mice showed decreased body weight, heart weight, and LV wall thickness compared to ad lib ob/ob mice. LV fractional shortening was decreased in ad lib ob/ob mice, but restored to WT levels in LR and CR groups. However, EM revealed severe cardiac steatosis in the CR-ob/ob group compared to only moderate steatosis in ad lib ob/ob . Despite marked cardiac steatosis, CR (like LR) restored mitochondrial coupling to WT levels. CR up-regulated genes associated with oxidative stress and cell death, changes suggestive of cardiac lipotoxicity. LR, but not CR was shown to induce core genes involved in glycerolipid/free fatty acid cycling, a highly thermogenic pathway that can reduce intracellular lipid stores. LR, but not CR up-regulated and restored PGC1 and PPARto wild type levels; CR paradoxically further suppressed cardiac PPAR. Thus, leptin is essential in protecting the heart from lipotoxicity, and the inability to up-regulate the thermogenic glycerolipid/free fatty acid cycling pathway may impair the response of leptin deficient animals to the lipotoxic stress of calorie restriction. 6 month aged ob/ob mice were either leptin repleted with osmotic mini-pumps, calorie restricted to match the caloric intake of the leptin repleted mice, or fed ad lib for one month. 6-8 month C57Bl/6J mice were aged to serve as controls.

Project description:Proteomic modifications linked to non-enzymatic glycation and glycoxidation are common in all tissues under hyperglycemic conditions, as present in metabolic syndrome, type 2 diabetes (T2D), mice bearing a homozygous mutation in leptin (so-called Ob/Ob mice, a common model of obesity and T2D) and mice subjected to a high fat diet (HFD). It has been already shown that the circulating levels of glycated or glycoxidated proteins (e.g., glycated hemoglobin or albumin) are commonly employed as a reliable indicator of overall glycemic status. Albeit these initial non-enzymatic reactions are reversible, following a series of chemical rearrangements protein glycation and glycoxidation become irreversible, generating the so-called advanced glycation end-products (AGEs). AGEs are commonly detected in tissue proteins with an extended half-life, including dermal collagens as well as extracellular matrix proteins. In these proteins, Nϵ-carboxymethyllysine (CML), pentosidins, and glucosepane represent the most prevalent AGEs. As an additional, novel mechanism linking protein PTMs to altered immunity, the research presented herein highlights that several components of the MHC class II antigen processing and presentation machinery are glycated in metabolic conditions associated with increased oxidative stress, leading to qualitative and quantitative changes in the MHC class II immunopeptidome. To investigate the impact of T2D and metabolic syndrome on the proteome of antigen presenting cells (APCs) we isolated dendritic cells (DCs, which are key for the initiation of antigen-specific immunity) from the lymph nodes of Ob/Ob mice and syngeneic, age-matched control C57BL/6 (B6) mice and mapped the oxidized proteins at the molecular and cellular level by employing label-free mass spectrometry using at least three biologically independent whole lysates of DCs. Analysis of the type of post-translational modifications (PTMs) accumulated in the proteome from the combined three biological Ob/Ob samples ranked the formyl-lysine and site-specific carboxymethylation on lysine (CML) as the most abundant AGEs found in the glycated proteome; with CML having about two-fold increase in their total PTM-modified spectral counts in the Ob/Ob vs control dendritic cell proteome. Additional glycoxidation-specific PTMs, that mapped only on the Ob/Ob proteome, albeit at a smaller amount than CML and formyl lysine, were glyceryl lysine and 3-deoxyglucosone. Finally, a separate proteomic analysis, performed on gradient purified late endosomes also mapped an increased number of PTM-modified proteins in the Ob/Ob organelles. Ingenuity pathway analysis (IPA) analysis identified metabolic pathways as well as phagocytosis, antigen processing and presentation and phagosome maturation amongst the top pathways including a higher number of proteins modified by AGEs or carbonylation in primary DCs from Ob/Ob vs. control mice. The site-specific amide-AGE modifications that we detected also mapped to proteins involved in response to DC signaling, immune cell trafficking, actin and cytoskeleton signaling, cell movement, and carbohydrate, nucleic acids and protein metabolism. Overall, these findings indicate that the DC proteome of Ob/Ob mice has an increased number of carbonyl PTMs and AGEs as compared to DC of C57BL/6 mice. The results presented herein are one of the first to map the redox mediated PTM in the primary mouse DC in healthy vs T2DM type syndrome physiological conditions.

			Action	DRS
	OB-R1.mgf	Mgf
	OB-R1.raw	Raw
	OB-R2.mgf	Mgf
	OB-R2.raw	Raw
	OB-R3.mgf	Mgf

Dataset Information

MS-based quantitative proteomic analysis of MAM from WT and obese mice.

Dataset's files

Publications

Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the <i>ob/ob</i> mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

MS-based quantitative proteomic analysis of MAM from WT and obese mice.

Dataset's files

Publications

Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the &lt;i&gt;ob/ob&lt;/i&gt; mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Structural and functional characterization of the cardiac mitochondria-associated reticular membranes in the <i>ob/ob</i> mouse model.