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The global obesity epidemic persists despite intensive study, partly because our conceptual framework for body weight regulation remains anchored in the energy balance model (EBM). This paradigm has struggled to reconcile the high heritability of body mass index (BMI) with the small effect sizes of common genetic variants. Here, I argue that a paradigm shift is required – one that moves from an energy-centric to a mass-centric view of metabolism. I propose that the mass balance model (MBM) provides a more precise framework for understanding the genetic architecture of obesity, focusing on the direct measurement of macronutrient fluxes. By dissecting the independent roles of fat, carbohydrate, and protein, we can reframe the function of key obesity genes. I analyze well-established genes like FTO and MC4R through the MBM lens and outline a path forward for nutrigenomics. This shift promises to resolve the "missing heritability" problem and pave the way for truly personalized metabolic health.