The formation of obesity prone rats may be associated with decreased HSL gene expression and increased LPL gene expression, which promote adipose synthesis and inhibit lipolysis.
Having both ADRB1 Gly389 allele and LPL Stop447 allele was associated with 71% (95% confidence interval: 26-89%) less odds for developing obesity from childhood to adulthood after adjusting for age, race, sex, and childhood BMI.
These results suggest that LPL gene S447X polymorphism modifies the relation between central obesity and serum lipids, which also stresses the importance of reducing waist circumference to improve serum lipids for people with central obesity, especially those with S/S447 genotype.
To determine whether changes in plasma lipids following a weight loss program were related to modifications in gene expression of the LDL receptor (LDL-R), lipoprotein lipase (LPL), and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, overweight/obese premenopausal women were recruited.
These results suggest that the nature of the mutation in the LPL gene modifies the relationship of HDL particle size to other metabolic variables and secondary factors such as abdominal obesity and gender.
For example, in mice both decreased lipoprotein lipase activities in adipose tissue and increased activity in muscle are associated with resistance to obesity; lack of lipoprotein lipase activity in macrophages is correlated with a decreased susceptibility to develop atherosclerotic lesions and overexpression of the enzyme in muscle is associated with increased blood glucose levels and insulin resistance.
Using both parametric and nonparametric methods, we found no evidence of linkage of obesity to any of nine candidate genes/regions, including the Prader-Willi chromosomal region (PWS), the human homologue of the mouse agouti gene (ASP), and the genes for leptin (OB), the leptin receptor (OBR/DB), the beta3-adrenergic receptor (ADRB3), lipoprotein lipase (LPL), hepatic lipase (LIPC), glycogen synthase (GYS), and tumor necrosis factor alpha (TNFA).
We conclude that genetic variants at the lipoprotein lipase locus occur commonly in subjects with this syndrome (four out of 18 subjects with probably functional mutants) and may affect the individual's response to obesity and diabetes mellitus for the development of lipaemia.
The data suggest that carriers for the LPL-N9 mutation have a mild genetic predisposition to developing hyperlipidaemia and an atherogenic lipid profile, but that this requires the presence of other genetic or environmental factors for full expression, one of which appears to be increasing obesity.