Depot-specific differences in perilipin and hormone-sensitive lipase expression in lean and obese.
BACKGROUND
Mainly dependent on hormone-sensitive lipase, lipolysis is differently impaired between fat depots in human obesity. Perilipin A expression is a critical element in adipocyte lipolysis. The present study aimed at comparing expression and subcellular distribution of perilipin and hormone-sensitive lipase in two abdominal adipose tissues of lean and obese women. We examined whether regional differences in perilipin expression contribute to impaired lipolytic rates.


METHODS
Abdominal subcutaneous and omental adipose tissues were obtained from six lean and ten obese women. We measured total protein content and relative distribution of hormone-sensitive lipase and perilipin proteins between lipid and non-lipid fractions in tissue homogenates. Hormone-sensitive lipase and perilipin mRNA levels, adipocyte size, basal (non-stimulated) and noradrenaline-stimulated lipolysis in isolated adipocytes were determined.


RESULTS
Adipocytes were significantly larger in the obese versus the lean women and in subcutaneous versus omental fat. Expressed as a function of cell number, basal lipolysis and noradrenaline responsiveness were higher in subcutaneous versus omental adipocytes from the obese women (P < 0.05). Despite higher or identical mRNA levels in the lean and the obese subjects and in subcutaneous and omental tissues, perilipin protein expression was lower in both depots in the obese versus the lean women, and in subcutaneous versus omental in both lean and obese women (P < 0.05). Perilipin was mostly (above 80%) present in the lipid fraction in both depots from the obese patients and the value decreased to 60% in the lean subjects (P < 0.05). Perilipin protein expression was inversely correlated to adipocyte size and basal lipolysis in both depots. Despite higher mRNA levels, hormone-sensitive lipase protein expression decreased in both depots of the obese women. Regional difference for hormone-sensitive lipase was reported in lipid fraction of subcutaneous fat of the obese subjects: hormone-sensitive lipase content was twice as low as in omental adipose tissue.


CONCLUSIONS
In both fat depots, a reduced perilipin protein expression was observed in women obesity. Perilipin protein level may contribute to differences in basal lipolysis and in adipocyte size between fat depots and may regulate lipid accumulation in adipocytes. Differences in hormone-sensitive lipase subcellular distribution were reported between fat depots in the obese women.
Ray
Hind
H
Department of Pathology and Cell Biology, Institute for Research in Immunology and Cancer, Université de Montréal, PO Box 6128, Station Centre-ville, Montréal Québec, H3C 3J7, Canada. hind.ray@umontreal.ca
Pinteur
Claudie
C
Frering
Vincent
V
Beylot
Michel
M
Large
Valérie
V
D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D015153:Blotting, Western; D002352:Carrier Proteins; D002469:Cell Separation; D048429:Cell Size / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000201:enzymology* / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*; D013851:Thinness / Q000201:enzymology* / Q000473:pathology
D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D012333:RNA, Messenger; D002787:Sterol Esterase; D009638:Norepinephrine