Disrupted citric acid metabolism inhibits hair growth

J Dermatol. 2022 Oct;49(10):1037-1048. doi: 10.1111/1346-8138.16509. Epub 2022 Jul 16.
Disrupted citric acid metabolism inhibits hair growth
Xiangguang Shi 1, Yahui Chen 1 2, Kai Yang 3, Yifei Zhu 1, Yanyun Ma 1, Qingmei Liu 1, Ji'an Wang 1, Chunya Ni 3, Yue Zhang 1, Haiyang Li 1, Jinran Lin 1, Jiucun Wang 1 4, Wenyu Wu 1 3

Hair follicles (HFs) play an essential role in sustaining a persistent hair growth cycle. The activities of dermal papilla cells (DPCs) and other cells inside the HFs dominate the process of hair growth. However, the detailed molecular mechanisms remain largely unknown. To investigate the role of citric acid (CA) metabolism in hair growth, we evaluated the effect of citrate synthase (CS)-CA axis on hair growth in vivo and in vitro. Mice hair growth was evaluated by morphology and histopathology analysis. The inflammation and apoptosis levels in mice, HFs, and DPCs were detected by immunohistofluorescence, qPCR, ELISA, western blot, and TUNEL assay. Cell proliferation, cell cycle, and cell apoptosis in DPCs were analyzed by real-time cell analysis and flow cytometer. We found that subcutaneous injection of CA in mice caused significant hair growth suppression, skin lesion, inflammatory response, cell apoptosis, and promotion of catagen entry, compared with the saline control, by activating p-p65 and apoptosis signaling in an NLRP3-dependent manner. In cultured human HFs, CA attenuated the hair shaft production and accelerated HF catagen entry by regulating the above-mentioned pathways. Additionally, CA hampered the proliferation rate of DPCs via inducing cell apoptosis and cell cycle arrest. Considering that citrate synthase (CS) is responsible for CA production and is a rate-limiting enzyme of the tricarboxylic acid cycle, we also investigated the role of CS in CA metabolism and hair growth. As expected, knockdown of CS reduced CA production and reversed CA-induced hair growth inhibition, anagen shrink, inflammation, and apoptosis both in HFs and DPCs. Our experiments demonstrated that CS-CA axis serves as an important mediator and might be a potential therapeutic target in hair growth.

Keywords: citrate synthase; citric acid; dermal papilla cell; hair follicle; hair growth.

The citric acid cycle, also known as the Krebs cycle or the tricarboxylic acid (TCA) cycle, is a series of biochemical reactions that take place in the mitochondria and produce energy and intermediates for biosynthesis from acetyl CoA
The citric acid cycle is regulated by several factors, such as the availability of substrates and products, the ratio of NAD + /NADH and ATP/ADP, and the activity of key enzymes.

Some conditions in the human body that could potentially disrupt the citric acid cycle are:

Hypoxia: A lack of oxygen in the tissues can impair the function of the electron transport chain, which is coupled to the citric acid cycle. This can result in a buildup of NADH and a depletion of NAD + , which can inhibit the citric acid cycle and reduce the production of ATP.

Diabetes: A high level of glucose in the blood can lead to an increased production of acetyl CoA from glycolysis and fatty acid oxidation. This can overwhelm the capacity of the citric acid cycle and cause a diversion of acetyl CoA into ketone bodies, which can cause ketoacidosis.

Disorders can affect the enzymes or cofactors involved in the citric acid cycle, such as pyruvate dehydrogenase, aconitase, or thiamine. This can impair the conversion of pyruvate to acetyl CoA, the synthesis of citrate, or the production of NADH and FADH 2 , respectively. These defects can cause various symptoms, such as lactic acidosis, neurological problems, or cardiomyopathy and Thiamine-responsive megaloblastic anemia syndrome.

I wonder if drinking too much pop and fruit juice increase our citric acid levels.

shaftless wrote:I wonder if drinking too much pop and fruit juice increase our citric acid levels.

Maybe what you meant was, would consuming excessive amounts of these disrupt the citric acid cycle?

Not really, but when you combine sugars with fats...that is the best way to put a wrench into the citric acid cycle.