Experimentally it was identified that systemic knockout mice for βK (Klb−/−) were protected against HF DIO.401 The lack of βK was found to shift BA pool composition to favor the classical pathway to produce a higher fraction of DCA, a highly potent TGR5 agonist.402 Reduced TGR5 agonism would result in reduced basal metabolic rate and reduced incretin release, predisposing for obesity. This evidence concerns the gene KNG1 and hydrops fetalis.