β-Aminoisobutyric acid (L-BAIBA) is a novel regulator of mitochondrial biogenesis and respiratory function in human podocytes

Abstract

Podocytes constitute an external layer of the glomerular filtration barrier, injury to which is a hallmark of renal disease. Mitochondrial dysfunction often accompanies podocyte damage and is associated with an increase in oxidative stress and apoptosis. β-Aminoisobutyric acid (BAIBA) belongs to natural β-amino acids and is known to exert anti-inflammatory and antioxidant effects. BAIBA has been reported to be involved in regulating mitochondrial dynamics, but unknown is whether BAIBA influences podocyte bioenergetics. The present study showed that human podocytes express the BAIBA receptor, Mas-related G protein-coupled receptor type D (MRGPRD), which is sensitive to BAIBA stimulation. The treatment of podocytes with L-BAIBA significantly increased their respiratory parameters, such as basal and maximal respiration, adenosine triphosphate (ATP) production, and spare respiratory capacity. We also found that L-BAIBA altered mitochondrial quantity, size, and shape, promoting organelle elongation and branching. L-BAIBA significantly upregulated peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) and transcription factor A mitochondrial (TFAM), indicating an increase in mitochondrial biogenesis. Our results demonstrate a novel regulatory mechanism of mitochondrial dynamics in podocytes, which may be important for maintaining their functions in the renal filtration barrier and prompting further investigations of preventing or ameliorating mitochondrial damage in podocytes in pathological states.

Molecular insights of exercise therapy in disease prevention and treatment

“…Although not investigated in the context of exercise, L-BAIBA was shown to induce mitochondrial biogenesis and improve respiratory function of podocytes via MRGPRD and phosphorylation of AMPK in the kidney. 194 This suggests a role of L-BAIBA in regulating glomerular function with potential applications in different nephropathies.…”

Molecular Insights into Transcranial Direct Current Stimulation Effects: Metabolomics and Transcriptomics Analyses

“…The metabolomic analysis revealed that tDCS affects 3-BAIBA and sphingosine, both of which are related to mitochondrial functioning [29][30][31] (Figure 2b). A gene expression analysis revealed that tDCS affects genes related to 'oxidative phosphorylation' and 'res-piratory chain reaction', which are key processes taking place in the mitochondria [15,18] (Figure 3d).…”

Exercise in Diabetic Nephropathy: Protective Effects and Molecular Mechanism

“…Some studies have proved that the exogenous treatment of BAIBA has a protective effect on kidney cells. Studies by Audzeyenka et al [133] showed that the exogenous supplementation of BAIBA in podocytes can improve their mitochondrial respiration efficiency, which may be related to the activation of PGC-1α and transcription factor A mitochondria (TFAM) to enhance mitochondrial biogenesis in podocytes. In another study, NRK-49F (normal rat kidney interstitial fibroblast cells) was treated with BAIBA, and BAIBA could significantly inhibit the proliferation and migration of NRK-49F.…”