Obesity and pancreatitis

Abstract

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.

FIGURE 1.

Abdominal imaging showing how location of fat influences the severity of pancreatitis. (a) MRI of a 50-year-old female (weight 85 kg, BMI 34.4) on the second day of biliary pancreatitis showing predominantly subcutaneous fat (yellow arrows) compared with visceral fat (area with yellow dots) with no fat necrosis. The patient had a mild course and was symptom free after 3 days of conservative management. (b) CT scan of a 83-year-old male (weight 84 kg, BMI 26.6) 2 weeks into alcoholic pancreatitis showing little subcutaneous fat (yellow arrows), but a large amount of visceral fat (dots in the peritoneal cavity). The fat around the pancreas was involved in peripancreatic fat necrosis (red dots), whereas the more distant visceral fat remained uninvolved (yellow dots). The clinical course was associated with early hypocalcemia (c), renal failure of >48 h (d) and the patient requiring ventilator support. AP, acute pancreatitis; CT, computerized tomography.

FIGURE 2.

Schematic showing how obesity associated IPF and PPF may, respectively, worsen pancreatic necrosis and lead to MSOF, along with therapeutic interventions (green) that may prevent this exacerbation. AP initiation results in lipase leakage from acinar cells (healthy acini shown in pink and blue, damaged ones orange). This lipase can hydrolyze the TG in IPF and PPF releasing UFAs. When released within the pancreas from IPF, UFAs can worsen pancreatic necrosis, or leak from visceral fat and cause systemic injury resulting in MSOF. AP, acute pancreatitis; IPF, intrapancreatic fat; MSOF, multisystem organ failure; PPF, peripancreatic fat; TG, triglyceride; UFA, unsaturated fatty acid.