Fig 2: Parallel PTH signaling pathways in control (Naca99S/S;Lrp6+/+;OCN-Cre) and compound heterozygous (Naca99S/A;Lrp6+/fl;OCN-Cre) littermates. Protein extracts were prepared from tibial shafts and immunoprobed for β-Catenin (A) and SIK2 (B). Equivalent loading was assessed by probing for α-Tubulin (C).

Fig 3: Body weight growth of the Sik2S587A mice fed chow or a high-fat diet. (a) Body weights of the male Sik2S587A mice at the age of 6 weeks. (b) Body weights of the female Sik2S587A mice at the age of 6 weeks. (c) Body weights of the male Sik2S587A mice at the age of 20 weeks. (d) Body weights of the female Sik2S587A mice at the age of 20 weeks. (e) Body weight gain of the male Sik2S587A mice from 6 weeks to 20 weeks of age. (f) Body weight gain of the female Sik2S587A mice from 6 weeks to 20 weeks of age. Two-way analysis of variance followed by Sidak’s test. All data are presented as the mean ± SEM. Male Sik2+/+ mice (chow n = 15, HFD n = 11). Male Sik2S587A/+ mice (chow n = 16, HFD n = 9). Male Sik2S587A/S587A mice (chow n = 6, HFD n = 7). Female Sik2+/+ mice (chow n = 12, HFD n = 12). Female Sik2S587A/+ mice (chow n = 16, HFD n = 15). Female Sik2S587A/S587A mice (chow n = 15, HFD n = 9).

Fig 4: SIK2 silencing attenuates glycolysis in colorectal cancer cell lines. The levels of (A) pyruvate kinase activity, lactate production and (B) glycolysis were detected using their corresponding kits. The mRNA and protein expression levels of the glycolysis-related genes, Glut1, HK2 and PKM2, were determined via (C) reverse transcription-quantitative PCR and (D) western blot analyses, respectively. **P<0.01, ***P<0.001 vs. siRNA-NC group. PKM2, pyruvate kinase M2; Glut1, glucose transporter 1; HK2, hexokinase 2; siRNA, small interfering RNA; NC, negative control.

Fig 5: Diagram showing the cAMP-SIK axis in adaptive thermogenesis of brown adipose tissue. There are no sympathetic inputs to brown adipocytes under thermoneutrality. PKA is inactive due to lower intracellular cAMP levels. Consequently, Sik2 is hypo-phosphorylated and becomes active, which leads to suppression of Ucp1 transcription. Under cold stimulation, catecholamines released from sympathetic nerves engage βARs (Adrb1–3), elevate intracellular cAMP levels and activate PKA in brown adipocytes through the activation of Gnas and adenylate cyclases. Then PKA phosphorylates and inhibits Sik2, which will promote Ucp1 transcription and ultimately adaptive thermogenesis.