Cholesterol Synthesis in Germfree and Conventional Rats

Abstract

The synthesis of cholesterol from labeled acetate and mevalonate by the liver and intestinal tract was investigated in germfree and conventional rats. When a low cholesterol diet was fed, the rates of in vitro synthesis from acetate by the liver, ileum and cecum of germfree rats were 13%, 11% and 25% of those of conventional rats, respectively. Cholesterol feeding markedly inhibited hepatic cholesterol synthesis from acetate in both germfree and conventional rats. Such inhibitions were released by additional cholestyramine feeding. The rate of hepatic cholesterol synthesis was greater and the liver cholesterol level was less after cholestyramine feeding in germfree rats than in conventional rats, suggesting an importance of bile acids in the regulation of cholesterol metabolism in the germfree rat. There was an inverse proportionality between the logarithmic rate of hepatic cholesterol synthesis and the liver cholesterol level in the germfree rat. Data indicate that endogenous cholesterol synthesis in the germfree rat may not be responsible for the high cholesterol level in plasma or liver and that the liver cholesterol level may play a major role in the regulation of hepatic cholesterogenesis in the germfree rat by a mechanism similar to that in the conventional rat.

Spatial and temporal regulation of sterol biosynthesis in Nicotiana benthamiana

“…). While such an approach is not without difficulties of interpretation, such as how does one account for differences in uptake of precursors by tissues from different developmental stages, this approach was successfully used to map the physiological control point for sterol metabolism in mammalian livers to between acetyl‐CoA and mevalonate (Siperstein and Guest , Ukai et al ). Also, previous work with plants demonstrated that SQS gene expression and enzyme activity were greatest in meristematic tissues (Devarenne et al ), suggesting sterol biosynthesis might be limited to newly divided cells (Diener et al ).…”

“…Second, and perhaps most significantly, early studies identified control imposed in the earlier steps of the pathway rather than in the later regions (Siperstein and Guest ). Thus, livers from animals transitioned from low cholesterol diets to high cholesterol showed a more immediate and dramatic decrease in radioactive acetate incorporation into sterols than mevalonate (Siperstein and Guest , Ukai et al ). Subsequent studies correlated this decline in liver sterol biosynthesis with an equal temporal and parallel decline in HMGR enzyme activity (Brown and Goldstein , Goldstein and Brown ).…”

Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4

“…The homeostasis of cholesterol, the substrate for BA synthesis, has also been studied. In germfree animals hepatic cholesterol synthesis from labeled acetate is only 13% of that of conventional animals [27]. When germfree rats are injected with cholesterol-26- 14 C they expire 50% less 14 C as 14 CO 2 than do conventional rats, with higher specific activities in plasma and liver [28].…”

Inhibition of cholesterol synthesis in mammary tissue, lung, and kidney following cholesterol feeding in the lactating rat

“…Approximately 200 mg of tissue was transferred to a 25 ml erlenmeyer flask which contained 3 ml of Krebs-Ringer phosphate buffer and 5 ~ Ci of [ 1A 4C] acetate (0.45 N Ci//~mole). The flasks were gassed with 95% 02-5% CO2, capped and incubated in a Dubnoff Metabolic Incubator (Precision Scientific Co., Chicago, IL)with 120 oscillations/min at 37 C for 2 hr, at which time 0.3 ml of 3N H2SO 4 was added through the stopper to terminate the incubation (12).…”

“…This method is discussed in detail elsewhere (12). Briefly, tissue slices were rinsed with an isotonic saline solution and transferred to screw cap culture tubes with 2 ml H 20.…”