The G-allele frequency of <i>KLB</i> rs7674434 and T-allele frequency of rs12152703 were higher in the obese with NAFLD than obese without NAFLD group (<i>P</i> = 0.004 and <i>P</i> = 0.006), but the genotype distribution between two non-obese groups did not differ.
However, further studies are needed to explore the possibility that Klotho could be a novel therapeutic target to reduce obesity and related complications, and to determine whether and how Klotho might influence the regulation and function of a related protein, β-Klotho, which is also involved in energy metabolism.
Recent microRNA (miR) studies have revealed that aberrantly elevated miR-34a in obesity directly targets β-Klotho, the obligate coreceptor for both FGF19 and FGF21, and attenuates metabolic signaling of these hormones.
Replenishment of recombinant FGF21 to a level equivalent to that in obesity restores SAT mass and reverses insulin resistance in FGF21KO, but not in adipose-specific βklotho knockout mice.
In addition to higher FGF21 levels, reduced KLB expression in liver and adipose tissue has been noted in these same individuals, suggesting that obesity may represent an FGF21 resistant state.
Since obesity has been reported to be associated with reduced expression of FGFR1 and βKlotho receptor in white adipose tissues in mice, our results suggest that the distribution in adipose tissues was influenced by target expression levels.