Fig 1.
SKO mice are lean and hyperphagic on a high fat diet.
(A) SKO mice are protected from weight gain on a high fat diet, (B) consume more food and (C) do not excrete more fat in feces.
Fig 2.
SKO mice demonstrate increased cholesterol efflux in whole skin, and decreased cholesterol levels in plasma.
(A) Cholesterol transport protein ABCA1 is increased in the skin of SKO mice on a HFD diet. (B) ABCA1 is asymmetrically localized around hair follicles (C) Total, HDL and LDL cholesterol fractions are decreased in plasma of SKO mice on a high fat diet.
Fig 3.
Cyp7b1, a rate-limiting enzyme of bile acid synthesis, is increased in whole-skin of SKO mice.
(A) Total bile acids are increased by 50% in SKO mice relative to controls. (B) The rate-limiting enzymes for hepatic bile acid synthesis cyp7a1 and cyp7b1 are unchanged whereas cyp7b1 in skin is increased. (C) Protein levels of cyp7a1 and cyp7b1 in liver and skin reflect mRNA levels. (D) Cyp7b1 protein expression is increased and localized around hair follicles.
Fig 4.
Bile acid composition is altered in SKO mice.
(A) Taurine-conjugated bile acids are increased; Tβ-MCA, a marker of extrahepatic bile acid synthesis, is most significantly increased. Hydrophobic bile acids are decreased (B) A pie chart representation of bile acid composition.
Fig 5.
On a high fat diet, enterohepatic circulation of bile acids is downregulated.
(A) Hepatic bile acid uptake and (B) export genes are downregulated and (c) bile acid transport genes are unchanged in the ileum.
Fig 6.
Bile acid-mediated thermogenesis is increased in SKO mice.
(A) On a HFD, bile acid signaling via Tgr5 and Dio2 is upregulated at the level of mRNA in brown adipose tissue. (B) Protein levels of TGR5 and (C) DIO2 (D) UCP1 and (E) oxidative phosphorylation proteins CII, CIII and CV are also significantly increased in brown adipose tissue. (F) Bile acid signaling via Tgr5 and Dio2 is increased in wild-type brown adipocytes treated with SKO plasma.