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This isn't speculative: radioligand binding assays conducted on human tissue samples show MC4R availability drops by approximately 35% during morning hours (6 AM12 PM) compared to evening baselines

It is indicated that renal tissues in the MetS population predominantly exhibit chronic lesions, including varying degrees of glomerulosclerosis, tubular atrophy, interstitial fibrosis, and atherosclerosis (44, 45)