title: Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src.
abstract: Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG)- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes-all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL) catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII) on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the Gq class of G proteins and the subsequent phospholipase C β4 (PLCβ4), protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome.
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Uchiyama
authors.affiliation: Gunma University School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Tomono
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.affiliation: Clinical Investigation Unit, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Medicine and Biological Science, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D000081247:CSK Tyrosine-Protein Kinase; D002478:Cells, Cultured; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000473:pathology; D054799:Phospholipase C beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D050151:Subcutaneous Fat / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014280:Triglycerides; D000804:Angiotensin II; C576887:ataxia telangiectasia and Rad3-related kinase, rat; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D064007:Ataxia Telangiectasia Mutated Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D008071:Lipoprotein Lipase; D054799:Phospholipase C beta; C518044:Plcb4 protein, rat; D043802:GTP-Binding Protein alpha Subunits, Gq-G11