The lipolytic enzyme hepatic lipase (HL) participates in providing cholesterol substrate for steroidogenesis. HL facilitates
selective uptake and mobilization of cholesterol by hydrolyzing phospholipids and triglycerides of high-density lipoprotein
(HDL) , which is the primary source of plasma cholesterol for rodent steroidogenic tissues . Both human and rodent
steroidogenic tissues have two different forms of HL expressed from a single gene. Extracellular HL is a 59-kDa
glycosylated enzyme expressed and secreted from parenchymal cells of the liver . The extracellular form is bound to
heparan sulfate proteoglycans on the vascular endothelium of the liver and steroidogenic tissues, especially within corpora
lutea of the ovary . Recently, an intracellular form of HL was found to be expressed primarily in steroidogenic tissues
. The intracellular form is a 47-kDa enzyme that is expressed from the same gene as the full-length form but lacks the first
two exons and signal sequence . In steroidogenic tissues, >90% of mRNA for HL codes for the truncated form;
therefore, little to no full-length extracellular HL is made within these tissues . The truncated HL retains the catalytic site
that is present in the extracellular HL. The expression of extracellular and intracellular HL forms by steroidogenic tissues
and their role in HDL metabolism suggest that HL participates in providing cholesterol to support steroidogenesis.
NCBI Summary:
LIPC encodes hepatic triglyceride lipase, which is expressed in liver. LIPC has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. [provided by RefSeq, Jul 2008]
General function
Enzyme
Comment
Cellular localization
Cytoplasmic
Comment
Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters. Pirwany IR et al. (2001) Women with polycystic ovary syndrome (PCOS) exhibit an abnormal lipoprotein profile, characterized by raised concentrations of plasma triglyceride, marginally elevated low density lipoprotein (LDL)-cholesterol, and reduced high density lipoprotein (HDL)-cholesterol. However, a normal LDL-cholesterol level may be misleading since LDL exists as subpopulations of particles differing in size and atherogenic potential. Smaller LDL particles are more atherogenic and high concentrations often occur in association with elevated circulating triglyceride concentrations (but frequently normal total LDL-cholesterol), increased hepatic lipase activity (HL) and insulin resistance. Information on LDL subclasses and HL activity in women with PCOS is sparse. The aim of this study was to determine the concentrations of small, dense LDL (LDL-III) in women with PCOS relative to body mass index (BMI)-matched controls. We also examined the association of lipoprotein subfraction concentrations with endogenous sex hormone concentrations, since existing literature suggested that androgens up-regulate and oestrogens down-regulate HL activity, a key determinant of LDL subfraction distribution. Cross sectional study. Fifty-two women with oligomenorrhoea and polycystic ovaries determined by ultrasound and BMI matched women with normal menstrual rhythm (NMR) and normal ovarian appearances (n = 14) were recruited from gynaecology clinics. Anthropometric data and fasting blood samples were obtained for metabolic, hormonal and LDL subfraction estimation and a heparin provocation test was used to estimate HL activity. Subjects with PCOS demonstrated higher waist:hip ratio (WHR), testosterone, triglyceride, VLDL-cholesterol concentrations, and HL activity (P < 0.05), whereas SHBG concentrations were significantly lower than controls. PCOS women had higher concentrations (38.0 vs. 25.0 mg/l; P = 0.026) and proportions (12.8 vs. 8.2%; P = 0.006) of small, dense LDL (LDL III), relative to controls. Within the PCOS group, plasma triglyceride and HL activity were the strongest univariate predictors of LDL III mass. They remained as independent predictors in multivariate analysis, and together accounted for 37% of its variability (P = 0.0002). Independent predictors of plasma triglyceride and HL in turn, were measures of fat distribution (waist circumference or WHR) and fasting insulin concentration. Serum testosterone concentration was not associated either in univariate or multivariate analysis with any of the measured lipid, lipoprotein or subfraction parameters, nor with HL activity in the women with PCOS. We conclude that women with polycystic ovary syndrome have increased hepatic lipase activity and mass and percentage of small, dense low density lipoprotein relative to body mass index-matched controls with normal menstrual rhythm and normal ovaries. Further, these metabolic perturbances appear related more closely to adiposity/insulin metabolism than to circulating androgen levels.//////////////////
Ovarian function
Follicle development, Steroid metabolism
Comment
Expression regulated by
LH
Comment
Ovarian localization
Comment
Vieira-van Bruggen D, et al 1997 reported that hepatic lipase gene expression is transiently induced by gonadotropic hormones in rat ovaries.
Hepatic lipase (HL) gene expression was studied in rat ovaries. A transcript lacking exons 1 and 2
could be detected by reverse transcription-polymerase chain reaction (RT-PCR) in the ovaries of
mature cyclic females and of immature rats treated with pregnant mare serum followed by human
chorionic gonadotropin (hCG) to induce superovulation. By competitive RT-PCR the HL transcript
was quantified. Low levels of HL mRNA were detected in ovaries of mature cyclic females and of
immature rats. During superovulation HL mRNA was several fold higher than in mature cyclic rats
and transiently increased to a maximum at 2 days after hCG treatment. Pulse-labelling of ovarian
cells and ovarian slices with [35S]methionine followed by immunoprecipitation with polyclonal
anti-HL IgGs showed de novo synthesis of a 47 kDa HL-related protein. Expression of the protein
was transiently induced by gonadotropins with a peak at 2 days after hCG treatment. Induction of
liver-type lipase activity occurred only after HL mRNA and synthesis of the HL-related protein had
returned to pre-stimulatory levels. The expression of the HL gene in ovaries is inducible and
precedes the expression of the mature, enzymatically active liver-type lipase.
Follicle stages
Preovulatory
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment:Wade RL et al 2002 reported that hepatic lipase deficiency attenuates mouse ovarian progesterone
production leading to decreased ovulation and reduced litter
size.
The lipolytic enzyme hepatic lipase (HL) may facilitate mobilization of
cholesterol substrate for ovarian steroidogenesis. breeding performance and ovarian responses to gonadotropins in HL-/- mice.
HL-/- female mice bred with HL-/- mates had the same pregnancy success rate
and. pup survival rate as did wild-type (WT) mice but had significantly
smaller litters, producing 1.7 fewer pups per litter. Mice were primed with
eCG/hCG, and at 6 h post-hCG the HL-/- mice had smaller ovaries than did the
WT mice. HL deficiency specifically affected ovarian weight; adrenal gland
weights did not differ between WT and HL-/- mice. HL-/- mice weighed more than
age-matched WT mice. Between the two mouse genotypes, uterine weights were the
same, indicating that estrogen production was equivalent. However, the HL-/-
ovaries produced significantly less progesterone than did the WT ovaries
within 6 h of hCG stimulation. HL-/- ovaries had the same number of large
antral follicles as did the WT ovaries but had fewer hemorrhagic sites, which
represent ovulations, fewer corpora lutea, and more oocytes trapped in corpora
lutea. We suggest that reduced progesterone synthesis following hCG
stimulation attenuated the final maturation of preovulatory follicles,
resulting in smaller ovaries. Furthermore, reduced progesterone production
limited the expression of proteolytic enzymes needed for tissue remodeling,
resulting in fewer ovulations with a corresponding increase in trapped or
unovulated oocytes and providing a possible explanation for the smaller litter
size observed in spontaneously ovulating HL-/- mice.