The liver X receptor (LXR) family is another group of transcription factors that sense lipids. It consists of LXRα and LXRβ. LXRα is primarily expressed in adipose tissue, liver, intestine, and kidney, while LXRβ is expressed ubiquitously. LXRs belong to the nuclear hormone receptor family and heterodimerize with RXR, similar to PPARs. LXRs act as cholesterol sensors. In conditions of high cholesterol, LXRs upregulate the expression of ATP-binding cassette (ABC) proteins. In the presence of excess cholesterol, LXRs also increase ABC protein expression in the gastrointestinal tract. This promotes the efflux of cholesterol from enterocytes to the lumen for excretion. Mutations in the transporters ABCG5 and ABCG8 result in sitosterolemia, which is characterized by excessive absorption of cholesterol and plant sterols. In the liver, LXRs promote the conversion of cholesterol to bile acids for excretion or to cholesterol esters for storage. In the latter action, LXRs increase SREBP1C expression, thereby increasing the fatty acylCoAs needed for esterification.
Genetic factors contribute to about 25% of the variability in total body fat and adipose tissue mass. This is supported by evidence such as the correlation between the body mass of adopted children and their biological parents rather than their adoptive parents, the greater similarity of adipose stores in identical twins compared to fraternal twins, and the greater correlation between weight gain and abdominal fat in identical twins compared to fraternal twins when they consume excess calories. Several genes associated with obesity have also been identified.
The gestational environment has a significant impact on the body mass of adults. The influence of maternal diet on the weight and body composition of offspring is known as fetal programming. Low birth weights are associated with an increased risk of obesity, cardiovascular disease, and diabetes. These findings suggest that fetal metabolism has the ability to adapt and be influenced by the in utero environment. The development of a "thrifty" metabolism would be advantageous for individuals born to mothers with limited resources.
Anotherfamilyoflipid-sensingtranscriptionfactorsistheliver X receptor (LXR) family,whichiscomposedofLXRα andLXRβ.LXRα isexpressedprimarilyinadiposetissue,liver,intestine,andkidney,whereasLXRβ isubiquitouslyexpressed.LXRsarerelatedtoPPARsinthattheyaremembersofthenuclearhormonereceptorfamilyandheterodimerizewithRXR.LXRsarecholesterolsensors.Inhigh-cholesterolconditions,LXRsupregulateexpressionofATP-bindingcassette(ABC)proteins.Inthefaceofexcesscholesterol,LXRsalsoincreaseABCproteinexpressioninthegastrointestinaltract,whichpromoteseffluxofcholesterolfromenterocytestothelumenforexcretion.Mutationsinthesetransporters(ABCG5andABCG8)causesitosterolemia, characterizedbyexcessiveabsorptionofcholesterolandplantsterols.Intheliver,LXRspromoteconversionofcholesteroltobileacidsforexcretionortocholesterolestersforstorage.Inthelatteraction,LXRsincreaseSREBP1Cexpression,therebyincreasingthefattyacylCoAsneededforesterification.
of body weight that is accounted for by adipose tissue. About 25% of the variance in total body fat appears to be due to genetic factors. A genetic influence on fat mass is supported by (1) the tendency for the body mass of adopted children to correlate better with that of their biological parents than with that of their adoptive parents; (2) the greater similarity of adipose stores in identical (monozygotic) twins, whether reared together or apart, than in fraternal (dizygotic) twins; (3) the greater correlation between gains in body weight and abdominal fat in identical twins than in fraternal twins when they are fed a caloric excess; and (4) the discovery of several genes that cause obesity.
In addition, the gestational environment has a profound effect on body mass of the adult. The effect of maternal diet on the weight and body composition of offspring is called fetal programming. Low birth weights correlate with increased risk for obesity, cardiovascular disease, and diabetes. These findings suggest that the efficiency of fetal metabolism has plasticity and can be altered by the in utero environment. The development of a “thrifty” metabolism would be advantageous to an individual born to a mother