Purpose of review: The obesity pandemic poses a unique set of problems for acute pancreatitis – both by increasing acute pancreatitis incidence, and worsening acute pancreatitis severity. This review explores these associations, underlying mechanisms, and potential therapies. Recent findings: We review how the obesity associated increase in gallstones, surgical, and endoscopic interventions for obesity management, diabetes, and related medications such as incretin-based therapies and hypertriglyceridemia may increase the incidence of acute pancreatitis. The mechanism of how obesity may increase acute pancreatitis severity are discussed with a focus on cytokines, adipokines, damage-associated molecular patterns and unsaturated fatty acid-mediated lipotoxicity. The role of obesity in exacerbating pancreatic necrosis is discussed; focusing on obesity-associated pancreatic steatosis. We also discuss how peripancreatic fat necrosis worsens organ failure independent of pancreatic necrosis. Last, we discuss emerging therapies including choice of intravenous fluids and the use of lipase inhibitors which have shown promise during severe acute pancreatitis. Summary: We discuss how obesity may contribute to increasing acute pancreatitis incidence, the role of lipolytic unsaturated fatty acid release in worsening acute pancreatitis, and potential approaches, including appropriate fluid management and lipase inhibition in improving acute pancreatitis outcomes.

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis–associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence of acute pancreatitis. Pancreatic triglyceride lipase (PNLIP) increased in adipose tissue during pancreatitis and entered adipocytes by multiple mechanisms, hydrolyzing adipose triglyceride and generating excess NEFAs. During pancreatitis, obese PNLIP-knockout mice, unlike obese adipocyte-specific ATGL knockouts, had lower visceral adipose tissue lipolysis, milder inflammation, less severe organ failure, and improved survival. PNLIP-knockout mice, unlike ATGL knockouts, were protected from adipocyte-induced pancreatic acinar injury without affecting NEFA signaling or acute pancreatitis induction. Therefore, during pancreatitis, unlike diverticulitis, PNLIP leaking into visceral adipose tissue can cause excessive visceral adipose tissue lipolysis independently of adipocyte-autonomous ATGL, and thereby worsen organ failure.

PA is an opportunistic pathogen that is commonly associated with severe infection in immunocompromised hosts. Siglec-9 binds with Sias by cis interaction on the neutrophil surface, thereby reducing immunological activity. However, neutrophils bind with pathogens through trans interactions of siglec-9 with Sias. Neutrophils kill invading pathogens by NETs, along with extracellular phagocytosis. Here, we report the mode of the adsorption of Sias by PA from host serum, the interaction of PA^+Sias with human neutrophils, and the resulting neutrophil immunological activity. The α2–3-linked sialoglycoproteins adsorbed by PA exhibited potent binding with the soluble siglec-9-Fc chimeras, CHO-siglec-9 and siglec-9 on neutrophils. The binding between PA^+Sias and neutrophils was blocked by the synthetic sialoglycan Neu5Acα2–3Galβ1–4GlcNAc, confirming the linkage-specific, Sias–siglec-9 interaction. The PA^+Sias and siglec-9 interaction on neutrophils reduced the level of ROS and the release of elastase, resulting in a reduction of NETs formation, demonstrating the role of the sialoglycoproteins adsorbed by PA in the weakening of neutrophil activity. The resistance of PA^+Sias to NETs was made evident by the increased survival of PA^+Sias. Moreover, the decrease in PA^−Sias survival demonstrated the involvement of NETs formation in the absence of the Sias–siglec-9 interaction. N-actylcysteine or sivelestat-pretreated neutrophils enhanced the survival of PA^−Sias. DNAse-pretreated neutrophils did not exhibit any NETs formation, resulting in the enhanced escape of PA^−Sias. Taken together, one of the survival mechanisms of PA^+Sias is the diminution of innate immunity via its adsorption of sialoglycoproteins by its engagement of the inhibitory molecule siglec-9. This is possibly a general mechanism for pathogens that cannot synthesize Sias to subvert immunity.

The opportunism of Pseudomonas aeruginosa (PA) in immunocompromised hosts prompted us to explore the potential role of sialic acids (Sia) in this phenomenon. Culture of PA in the presence of exogenous Sia resulted in linkage‐specific incorporation of Sia which was associated with decreased complement deposition on the bacteria. Sia acquired by PA mediated enhanced binding of bacteria to recombinant‐CHO cells expressing human siglec‐7 or siglec‐9, as well as to human NK‐cells and monocytes naturally expressing these siglecs. Therefore, Sia may be acquired by PA in the host and contribute to bacterial pathogenicity and host‐cell interactions via reduction of complement deposition and siglec‐dependent recognition.

Saturated fat breaks down less during sudden illnesses, resulting in lower monomer concentrations, and reducing disease severity.

While most COVID-19 patients clear the infection, some develop severe disease with organ failure. Based on patterns associated with severe COVID-19, underlying mechanisms, we propose a simple, low risk supportive intervention.