Depot-specific regulation of perilipin by rosiglitazone in a diabetic animal model.
Treatment with rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR) gamma agonist, results in lipid storage coupled with reduced release of free fatty acids into the circulation. Many studies have reported that PPAR-gamma agonists increase subcutaneous adiposity but have no effect on visceral fat mass. Perilipin, a family of phosphoproteins that coat intracellular lipid droplets in adipocytes, is essential for enlargement of lipid droplets. Recently, a functional PPAR-responsive element was identified within the murine perilipin gene. We hypothesized that the depot-specific regulation of perilipin by rosiglitazone may be associated with the fat-redistribution and insulin-sensitizing effects of rosiglitazone. After 6 weeks of rosiglitazone treatment in Otusuka Long-Evans Tokushima Fatty rats, an animal model of type 2 diabetes mellitus, we measured changes in adiposity, triglyceride content in liver and muscle, morphology of the pancreas, and perilipin messenger RNA and protein expression in adipose tissue. Rosiglitazone increased subcutaneous adiposity, decreased triglyceride content of liver and muscle, decreased plasma free fatty acids (2107 +/- 507 micromol/L in the placebo group vs 824 +/- 148 micromol/L in the rosiglitazone group; P < .05), and improved insulin resistance. The islets of placebo-treated rats showed hypertrophy and destruction, whereas the islets of rosiglitazone-treated rats showed hypertrophy, but the islet architecture remained intact. Perilipin messenger RNA and protein expression increased in subcutaneous fat, but did not change in visceral fat, after rosiglitazone treatment. In 3T3-L1 cells, rosiglitazone pretreatment decreased lipolysis and increased perilipin protein. In conclusion, increased perilipin expression in subcutaneous fat after rosiglitazone treatment is likely to be a mediator of reduced lipolysis, resulting in lipid storage in subcutaneous fat, fat redistribution, and insulin sensitization.
Kim
Hae Jin
HJ
Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea.
Jung
Tae Woo
TW
Kang
Eun Seok
ES
Kim
Dae Jung
DJ
Ahn
Chul Woo
CW
Lee
Kwan Woo
KW
Lee
Hyun Chul
HC
Cha
Bong Soo
BS
D041721:3T3-L1 Cells; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D020334:Rats, Inbred OLETF; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D000070778:Perilipin-1; D010750:Phosphoproteins; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D012313:RNA