Pekcec, A. | bioRxiv Science

bioRxiv2025

The obesity-linked peptide SP16 regulates adipocytes through GIP and insulin receptor

Obesity has emerged as a global epidemic and represents a major public health concern due to its profound implications for metabolic diseases. While recent pharmacological interventions primarily aim to reduce food intake, enhancing energy expenditure in adipose tissue offers a promising complementary approach. In this study, we identify that SP16, a synthetic 1- antitrypsin derived peptide, is a novel GIP (gastric inhibitory peptide) receptor agonist. SP16 promotes lipolysis via the cAMP pathway, resulting in increased mitochondrial oxygen consumption in adipocytes. Furthermore, SP16 binds to the insulin receptor, and at high concentrations, it attenuates insulin receptor signaling. In diet-induced obese (DIO) mice, acute SP16 treatment improved glucose clearance, elevated circulating free fatty acids, and decreased leptin levels. Ex vivo analyses of epididymal white adipose tissue corroborated these findings, demonstrating enhanced lipolysis in SP16-treated mice. In conclusion, SP16 emerges as a novel lipolytic peptide with beneficial metabolic effects. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/660082v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@135f172org.highwire.dtl.DTLVardef@7e8152org.highwire.dtl.DTLVardef@15c6937org.highwire.dtl.DTLVardef@1ffc295_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with Biorender.com

pharmacology and toxicology↗

bioRxiv2024

Excitatory neurons of the anterior cingulate cortex encode chosen actions and their outcomes rather than cognitive state

The anterior cingulate cortex (ACC) causally influences cognitive control of goal-directed behaviour. However, it is unclear whether ACC directly encodes cognitive variables like attention or impulsivity, or implements goal-directed action selection mechanisms that are modulated by them. We recorded ACC activity with miniature endoscopic microscopes in mice performing the 5-choice-serial-reaction time task, and applied decoding and encoding analyses. ACC pyramidal cells represented specific actions before and during the behavioural response, whereas the response type (e.g. correct/incorrect/premature) - indicating the state of attentional and impulse control - could only be decoded during and after the response with high reliability. Devaluation and extinction experiments further revealed that action encoding depended on reward expectation. Our findings support a role for ACC in goal-directed action selection and monitoring, that is modulated by cognitive state, rather than in tracking levels of attention or impulsivity directly in individual trials.

neuroscience↗