Transmembrane protein 126B protects against high fat diet (HFD)-induced renal injury by suppressing dyslipidemia via inhibition of ROS

Area of Science:

• Nephrology
• Metabolic Diseases
• Molecular Biology

Background:

• High-fat diet (HFD) consumption can lead to metabolic syndrome and chronic kidney disease (CKD).
• The precise mechanisms underlying HFD-induced kidney injury remain incompletely understood.
• Transmembrane protein 126B (Tmem126b), a complex I assembly factor, plays a role in cellular processes.

Purpose of the Study:

• To investigate the role of Tmem126b in the pathogenesis of HFD-induced kidney injury.
• To elucidate the molecular mechanisms by which Tmem126b influences renal damage in response to HFD.
• To determine if Tmem126b is a potential therapeutic target for HFD-induced CKD.

Main Methods:

• Utilized a mouse model fed a high-fat diet (HFD) to induce metabolic disorders and kidney injury.
• Generated and analyzed Tmem126b knockout (KO) mice under HFD conditions.
• Employed cell culture experiments with palmitate (PA) and Tmem126b knockdown to validate findings.
• Assessed kidney damage, metabolic parameters, inflammation, oxidative stress, and mitochondrial function.

Main Results:

• Tmem126b expression was elevated in the kidneys of HFD-fed mice.
• Tmem126b knockout attenuated HFD-induced metabolic disorders and alleviated kidney damage.
• Tmem126b deletion prevented HFD-induced dyslipidemia, apoptosis, and mitochondrial dysfunction by regulating associated signaling pathways.
• Tmem126b knockout ameliorated renal inflammation via repression of nuclear factor kappa B (NF-κB) signaling and reduced oxidative stress by promoting nuclear factor-erythroid 2 related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) expression.
• Inhibition of Nrf-2 abolished the protective effects of Tmem126b knockdown against palmitate-induced cellular damage.

Conclusions:

• Tmem126b acts as a positive regulator in the progression of HFD-induced CKD.
• Tmem126b deletion protects against HFD-triggered renal injury by modulating lipid deposition, apoptosis, inflammation, oxidative stress, and mitochondrial dysfunction, partly through regulating Nrf-2 expression.
• Targeting Tmem126b may offer a novel therapeutic strategy for managing HFD-induced kidney disease.