Hormonal
Soluble GPNMB (sGPNMB) promotes lipogenesis in white adipose tissue by activating SREBP1c via CD44 binding, thereby acting as a risk factor for obesity progression.
This research highlights that obesity involves complex signaling where soluble proteins released by fat cells can drive further fat storage. While not a direct lifestyle intervention, understanding this mechanism underscores why reducing adiposity (via caloric deficit and exercise) is crucial, as it reduces the source of these pro-lipogenic signals.
sGPNMB was also described as a hepatokine that activates SREBP1c and thus lipogenesis in obese WAT by binding CD44 on adipocytes, resulting in a positive correlation between sGPNMB and BMI [86]. These findings indicate that GPNMB is a strong risk factor for obesity.
Why this rating
The paper is a review summarizing multiple studies (mostly murine models); direct human clinical trial data for this specific mechanism is not the primary focus.
Source
Glycoprotein Non-Metastatic Protein B (GPNMB): The Missing Link Between Lysosomes and Obesity
Valentina Bianco et al. · Experimental and Clinical Endocrinology & Diabetes · 2023
DOI 10.1055/a-2192-0101
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