PPARs modulate cardiac metabolism and mitochondrial function in diabetes

Lee, Ting-Wei; Bai, Kuan Jen; Chao, Tze Fan; Kao, Yu Hsun; Chen, Yi Jen

doi:10.1186/s12929-016-0309-5

Cited by 83 publications

(64 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some authors speculate that the upregulation of the nuclear receptor transcription factor PPARα and its coactivators PGC-1α/β is one of the preliminary requirements for metabolic switch from glucose to FA consumption in IR and diabetic hearts (Schilling, 2015 ; Lee et al, 2017 ). This agrees with an increased level of PPARα as well as the total (+38%) and sarcolemmal (+26%) FAT/CD36 content in the diabetic animal hearts (Mansor et al, 2017 ).…”

Section: Fatty Acid Transporter Proteinsmentioning

confidence: 99%

The Implication of PGC-1α on Fatty Acid Transport across Plasma and Mitochondrial Membranes in the Insulin Sensitive Tissues

2017

View full text Add to dashboard Cite

PGC-1α coactivator plays a decisive role in the maintenance of lipid balance via engagement in numerous metabolic processes (i.e., Krebs cycle, β-oxidation, oxidative phosphorylation and electron transport chain). It constitutes a link between fatty acids import and their complete oxidation or conversion into bioactive fractions through the coordination of both the expression and subcellular relocation of the proteins involved in fatty acid transmembrane movement. Studies on cell lines and/or animal models highlighted the existence of an upregulation of the total and mitochondrial FAT/CD36, FABPpm and FATPs content in skeletal muscle in response to PGC-1α stimulation. On the other hand, the association between PGC-1α level or activity and the fatty acids transport in the heart and adipocytes is still elusive. So far, the effects of PGC-1α on the total and sarcolemmal expression of FAT/CD36, FATP1, and FABPpm in cardiomyocytes have been shown to vary in relation to the type of PPAR that was coactivated. In brown adipose tissue (BAT) PGC-1α knockdown was linked with a decreased level of lipid metabolizing enzymes and fatty acid transporters (FAT/CD36, FABP3), whereas the results obtained for white adipose tissue (WAT) remain contradictory. Furthermore, dysregulation in lipid turnover is often associated with insulin intolerance, which suggests the coactivator's potential role as a therapeutic target.

show abstract

Section: Fatty Acid Transporter Proteinsmentioning

confidence: 99%

The Implication of PGC-1α on Fatty Acid Transport across Plasma and Mitochondrial Membranes in the Insulin Sensitive Tissues

2017

View full text Add to dashboard Cite

show abstract

“…PPARs are transcription factors that increase the expression of genes involved in fatty acid oxidation. On the other hand, the expression of several genes involved in glucose catabolism are decreased by PPARs ( 2 , 10 ).…”

Section: The Metabolic Flexibility Of the Healthy Heartmentioning

confidence: 99%

The Regulation of Insulin-Stimulated Cardiac Glucose Transport via Protein Acetylation

Renguet

Bultot

Beauloye

et al. 2018

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Cellular catabolism is the cell capacity to generate energy from various substrates to sustain its function. To optimize this energy production, cells are able to switch between various metabolic pathways in accordance to substrate availability via a modulation of several regulatory enzymes. This metabolic flexibility is essential for the healthy heart, an organ requiring large quantities of ATP to sustain its contractile function. In type 2 diabetes, excess of non-glucidic nutrients such as fatty acids, branched-chain amino-acids, or ketones bodies, induces cardiac metabolic inflexibility. It is characterized by a preferential use of these alternative substrates to the detriment of glucose, this participating in cardiomyocytes dysfunction and development of diabetic cardiomyopathy. Identification of the molecular mechanisms leading to this metabolic inflexibility have been scrutinized during last decades. In 1963, Randle demonstrated that accumulation of some metabolites from fatty acid metabolism are able to allosterically inhibit regulatory steps of glucose metabolism leading to a preferential use of fatty acids by the heart. Nevertheless, this model does not fully recapitulate observations made in diabetic patients, calling for a more complex model. A new piece of the puzzle emerges from recent evidences gathered from different laboratories showing that metabolism of the non-glucidic substrates induces an increase in acetylation levels of proteins which is concomitant to the perturbation of glucose transport. The purpose of the present review is to gather, in a synthetic model, the different evidences that demonstrate the role of acetylation in the inhibition of the insulin-stimulated glucose uptake in cardiac muscle.

show abstract

“…Reducing PGE2 production by INDO inhibited M2 polarization thus INDO shared a similar PPARG activation response with AA ( Fig 4F). To formally address the possibility of PPARG bridging AA/PGE2 mediated M2 macrophage polarization, we isolated bone marrow derived monocytes (BMDM) from wild type (WT, Pparg (Lee et al, 2017). Collectively, these data revealed that PGE2 enhanced OXPHOS during M2 polarization and PPARG de-activation participated in this process.…”

Section: Pge2 Inhibits Pparg Resulting In M2 Macrophage Polarizationmentioning

confidence: 99%

“…Metabolic reprogramming of tumor microenvironment (TME) by cancer cells provide a perfect example of how metabolism interplay with immune function (Pavlova and Thompson, 2016). Cancer cells released lactate, glutamine, succinate and α-ketoglutarate (α-KG) help T cell and macrophage polarize towards immunosuppressive phenotype (Angelin et al, 2017, Chen et al, 2017, Mehla and Singh, 2019. In contrast, metabolic reprogramming of the TAM inhibited tumor progression by allowing the accumulation of T cell receptor engineered T cells (Stromnes et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Arachidonic acid metabolism controls macrophage alternative activation through regulating oxidative phosphorylation in PPARG dependent manner

Wang

Jia

et al. 2020

Preprint

View full text Add to dashboard Cite

Macrophages polarization is mainly controlled by metabolic reprogramming in microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophages polarization models, we revealed a pivotal role for arachidonic acid metabolism in controlling the polarization of M1 and M2 macrophages. We demonstrated that M2 macrophage polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARG bridges these two unconnected processes via modulating oxidative phosphorylation. These results highlight the critical role of arachidonic acid metabolism as an immune regulator in modulating metabolic homeostasis and pathological process.

show abstract

PPARs modulate cardiac metabolism and mitochondrial function in diabetes

Cited by 83 publications

References 77 publications

The Implication of PGC-1α on Fatty Acid Transport across Plasma and Mitochondrial Membranes in the Insulin Sensitive Tissues

The Implication of PGC-1α on Fatty Acid Transport across Plasma and Mitochondrial Membranes in the Insulin Sensitive Tissues

The Regulation of Insulin-Stimulated Cardiac Glucose Transport via Protein Acetylation

Arachidonic acid metabolism controls macrophage alternative activation through regulating oxidative phosphorylation in PPARG dependent manner

Contact Info

Product

Resources

About