**Addendum 1**

unstable, when threatened by 'disease states', like NAFLD/NASH, than systems found in the osteoblast, which apparently appears more resilient to change, when exposed to condi-

Finally, it should be emphasized that bioinformatics analyses of the 'NRI2‐relative' NR1I3, the constitutive androstane receptor (CAR), which interacts with NR1I2 = SXR = PXR, is also biologically interfering with many of the same factors (e.g. PPARα, CEPBα, STATs and T3) [24], thus linking them together in a very tight regulatory network, affecting lipid metabolism. Understanding the impact of vitamin K2 on these regulatory systems seems to be mandatory to grasp and acknowledge the idea that this fat‐soluble molecule exerts such a tremendous effect on biological processes compatible with organ health, disease free old age, and thus 'longevity'.

**Figure 5.** MicroRNAs, transcription factors and 'functional' genes related to liver function in patients with NAFLD/ NASH with or without metabolic cardiovascular disease (see Refs. [21–23]). The three charts represent decreasing stringency/from top to bottom), and it should be emphasized that the regulatory system does not contain any reciprocal regulatory feedback systems, as was shown for the 'stabilization' of the osteoblast (or mineralizing

tions where inflammation prevails.

16 Vitamin K2 - Vital for Health and Wellbeing

phenotype).

#### **List of microRNAs and genes used as 'input' into the Mir@nt@n‐algorithm, asking the pro‐ gram to 'retrieve' regulatory networks**
