Visceral fat lipolysis by pancreatic lipases worsens heart failure.

ABSTRACT: Heart failure can be worse when associated with obesity, elevated serum pancreatic enzymes, elevated non-esterified fatty acids (NEFAs), or acute pancreatitis (AP). To understand this, here we study doxorubicin-induced heart failure, experimental AP, or pancreatic lipase-induced visceral fat necrosis in lean, genetically obese (ob/ob), or dual ob/ob pancreatic triglyceride lipase (PNLIP)-knockout mice. NEFA generation and resulting cardiac injury are measured. We note that ob/ob mice develop fat necrosis containing PNLIP and phospholipase A₂. This generates excess NEFAs that worsen cardiac injury, cause hypotension, and reduce survival. All these are prevented by PNLIP deletion or pharmacologic inhibition. Live imaging shows that phospholipase A₂ damages adipocyte mem

SUBMITTER: Smichi N 

PROVIDER: S-EPMC12208342 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature