DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration.

Planarians have a remarkable ability to undergo whole-body regeneration. Successful regeneration outcome is determined by processes like polarity establishment at the wound site, which is followed by pole (organizer) specification. Interestingly, these determinants are almost exclusively expressed by muscles in these animals. However, the molecular toolkit that enables the functional versatility of planarian muscles remains poorly understood. Here we report that SMED_DDX24, a D-E-A-D Box RNA helicase, is necessary for planarian survival and regeneration. We found that DDX24 is enriched in muscles and its knockdown disrupts muscle fiber organization. This leads to defective pole specification, which in turn results in misregulation of many positional control genes specifically during regeneration. ddx24 RNAi also upregulates wound-induced Wnt signalling. Suppressing this ectopic Wnt activity rescues the knockdown phenotype by enabling better anterior pole regeneration. To summarize, our work highlights the role of an RNA helicase in muscle fiber organization, and modulating amputation-induced wnt levels, both of which seem critical for pole re-organization, thereby regulating whole-body regeneration.

Sesaminol induces brown and beige adipocyte formation through suppression of myogenic program.

Adipocytes are key players in maintaining energy homeostasis and are classified into two different categories: white and brown adipocytes. While white adipocytes store energy as triacylglycerols in lipid droplets, brown adipocytes combust excess chemical energy and release in the form of heat through uncoupled respiration. This characteristic phenomenon of brown fat attracts researchers and pharmacological industries to view brown fat as one of the potential therapeutic targets for obesity and associated metabolic disease. In the current study, we investigated the effect of a small molecule, sesaminol (SML) on brown fat activity and found that SML induces the thermogenic program in primary white adipocytes as well as chow diet fed mice. In particular, SML treatment to mice elevated mitochondrial complex proteins and the rate of oxygen consumption in brown and white fat. Administration of SML to high fat diet (HFD) challenged mice decreased weight gain, adiposity and cholesterol levels along with an increase of brown fat gene program in brown and white fat. Mechanistically, SML repressed the myogenic gene program in C2C12 myoblasts and increased all mitochondrial marker genes as appeared in brown adipose cells. Together, our results demonstrate that SML stimulates brown adipose function and protects mice against diet-induced weight gain.

Sesaminol diglucoside, a water-soluble lignan from sesame seeds induces brown fat thermogenesis in mice.

Brown adipose tissue (BAT) is the site of non-shivering thermogenesis in mammals, wherein energy is dissipated as heat. We observed that aqueous extract of black sesame seed triggers an increase in the expression of Uncoupling Protein 1 (UCP1) in brown adipocytes from mice. The active component from the extract was purified and identified to be sesaminol diglucoside (SDG). SDG treatment decreased mass of white fat pads and serum glucose levels and increased UCP1 levels in BAT thereby protecting mice against high fat induced weight gain. Further in silico and in vitro studies revealed that these effects are due to the agonist like behaviour of SDG towards beta 3 adrenergic receptors (ß3-AR). Together, our results suggest that SDG induces BAT mediated thermogenesis through ß3-AR and protects mice against diet-induced obesity.