How to increase thermogenin-1

Thermogenin-1, also known as uncoupling protein 1 (UCP1), plays a crucial role in thermogenesis—the process of heat production in organisms.

In a discussion on the Lex Fridman Podcast, Manolis Kellis explains that thermogenesis can be regulated explicitly and can be turned on or off. This regulation involves components like RX5 and RX10, which are master regulators of thermogenesis versus lipogenesis (fat generation). When you eat too much, these regulators can help burn calories as heat in fat cells 1.

Understanding and manipulating these genetic and regulatory processes could potentially enhance thermogenesis. For example, pharmaceutical interventions or genetic editing techniques like CRISPR-Cas9 could enable control over these pathways, effectively switching between fat-storing and fat-burning phenotypes. This could be achieved by targeting specific genes and mutations involved in these regulatory mechanisms, thereby enhancing thermogenic capacity 1.

Manolis Kellis explains that RX5 and RX10 are master regulators in the process of thermogenesis (heat production) versus lipogenesis (fat creation). These regulators, when functioning correctly, allow the body to burn excess calories as heat in fat cells. Essentially, RX5 and RX10 help in deciding whether energy should be stored as fat or burned off as heat.

The regulation process involves genetic mechanisms. Mutations in specific genes, such as the Rs142-1085 allele, can hinder the ability of RX5 and RX10 to function properly. In particular, a mutation that changes a nucleotide from T to C can prevent the regulatory protein RX5B from binding, thereby inhibiting the activation of thermogenesis 1.

To manipulate this process, interventions like CRISPR-Cas9 could be used to edit genes at the nucleotide level. This editing can flip cells from a fat-storing to a fat-burning state, thereby influencing the overall metabolic process. Such regulatory mechanisms can be targeted pharmaceutically or genetically to manage conditions like obesity by enhancing the body's natural ability to burn calories 1.