# The metabolic advantage of being young and male in obesity treatment outcomes in mice

## TL;DR

Young male mice have better weight loss outcomes than older females due to improved fat tissue response and gene activity.

## Contribution

This study identifies age and sex as critical factors influencing weight loss outcomes through WAT transcriptomic plasticity in mice.

## Key findings

- Male sex and youth are linked to better WAT mobilization and improved weight loss outcomes.
- Aging impairs WAT transcriptomic plasticity and reduces the effectiveness of weight loss interventions.
- Weight loss is associated with gene expression changes in IL17, ACE2, lipolysis, and adipocyte differentiation pathways.

## Abstract

Although diversity in clinical trials is important to test the efficacy of a treatment, weight loss trials rarely account for age and sex. To highlight this deficiency, we set out to test whether age and sex affect WAT mobilization after weight loss surgery or intermittent fasting, in an obese mouse model. Here we show that male sex, youth, and WAT transcriptomic plasticity are characteristics associated with improved weight loss outcomes. Conversely, aging impairs WAT mobilization and transcriptomic plasticity. Greater surgical weight loss is associated with changes in the expression of genes relevant to the IL17 inflammatory signaling pathway, angiotensin converting enzyme 2 (ACE2) signaling, lipolysis, carbohydrate metabolism and adipocyte differentiation. In conclusion, female sex and older age appear to hinder molecular processes necessary for the reversal of WAT expansion. Future studies should examine the relevance of these findings to human obesity therapeutics.