Hormonal
Obesity-associated low-grade inflammation and adipose tissue dysfunction can induce resistance to β3-adrenergic receptor agonists (like CL316243) by suppressing β3-AR expression via the EPAC/RAP2A signaling pathway, thereby blunting thermogenic efficacy.
If you have obesity-related inflammation, standard fat-burning medications that target specific receptors (like β3-agonists) might be less effective because your body's inflammatory state can block these receptors. This highlights why some people don't respond to certain treatments and why newer drugs with different mechanisms might be needed.
The efficacy of CL316243 appears also to be reduced in the presence of obesity-associated low-grade inflammation... as obese mice with adipose tissue dysfunction and increased proinflammatory cytokines showed impaired β3-AR sensitivity to CL316243, leading to catecholamine resistance and reduced EE.
Why this rating
Based on animal models described in the review.
Source
Pharmacological modulation of adaptive thermogenesis: new clues for obesity management?
Valentina Annamaria Genchi et al. · Journal of Endocrinological Investigation · 2023
DOI 10.1007/s40618-023-02125-0
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