Association between intra-pancreatic fat deposition and diseases of the exocrine pancreas: A narrative review

Table 1 Nomenclature of the fat in the pancreas

Name	Definition
Pancreatic steatosis	The description of fat accumulation in the pancreatic gland
Fatty pancreas	Fatty accumulation in the pancreas
Pancreatic lipomatosis	The most frequent benign pathologic condition of the adult pancreas
Fatty infiltration of the pancreas	Deposition of a large amount of fat in the pancreas
Nonalcoholic fatty pancreas disease	The accumulation of fat in pancreatic tissue (located within adipocytes)
Intra-pancreatic fat deposition	Diffuse presence of fat (measured on a continuous scale) within the pancreas; excludes peri-pancreatic (extra-lobular) fat

Table 2 Disease

Disease	Mechanism	Ref.
Pancreatitis	Inflammation induced by fat deposition and adipokine secreted by adipose tissue promote the occurrence and development of pancreatitis	Sbeit and Khoury[58], 2021; Tirkes et al[64], 2019
Pancreatic cancer	The inflammatory process of the pancreas in the context of fatty pancreas is an important inducible factor, and the different types of fatty infiltration of the pancreas also play a role in the different processes of tumor development	Frendi et al[9], 2024; Lilly et al[75],2023
Exocrine dysfunction	Lipids have affected acinar cells or replaced lost acinar cells and necrotic apoptotic endocrine tissue	Tahtacı et al[77], 2018
POPF	IPFD increases the softness of the pancreatic glands and raises the risk of POPF	Gaujoux et al[79], 2010; Dei et al[81], 2022
Type 2 diabetes mellitus	IPFD leads to dysfunction of islet beta cells, affecting insulin secretion and exacerbating insulin resistance	Lu et al[83], 2019; Chin et al[84], 2021
Metabolic syndrome	IPFD is associated with components of metabolic syndrome such as obesity, hyperglycemia, dyslipidemia, etc	Smits and van Geenen[82], 2011
Cardiovascular disease	IPFD is associated with abnormal fat distribution and metabolic disorders throughout the body, which may affect the development of atherosclerosis	Kim et al[85], 2014

IPFD: Intrapancreatic fat deposition; POPF: Postoperative pancreatic fistula.

Table 3 Summary of intrapancreatic fat deposition treatment methods

Treatment method	Category	Mechanism of action	Research evidence	Ref.
Low-calorie diets	Non-pharmacological	Reduces insulin secretion and decreases adipose tissue accumulation in the pancreas and body	Evidence indicates that low-carbohydrate diets effectively diminish pancreatic and visceral fat deposition in individuals with obesity and type 2 diabetes	Taylor et al[122], 2018
Exercise	Non-pharmacological	Enhances overall insulin sensitivity and reduces pancreatic fat content	Numerous small clinical trials have demonstrated that physical activity can lower pancreatic fat deposition, regardless of the baseline glucose tolerance of participants	Heiskanen et al[121], 2018
Lactoferrin	Non-pharmacological	Improves lipid profiles, pancreatic function, and histological integrity	Supplementation with lactoferrin has been shown to mitigate weight gain, improve lipid levels, and enhance pancreatic function in models fed a high-fat diet	Hassan et al[123], 2022
Metformin	Pharmacological	Improves insulin resistance and reduces pancreatic and overall adipose tissue	In studies involving high-fat diet-fed mouse models, metformin significantly decreased pancreatic fat deposition and ameliorated insulin resistance	Souza-Mello et al[128], 2010
GLP-1 receptor agonists	Pharmacological	Stimulates insulin secretion, inhibits glucagon release, promotes weight loss, and decreases pancreatic fat	A growing body of clinical and preclinical evidence supports the efficacy of GLP-1 receptor agonists in reducing fat accumulation in both the pancreas and liver while enhancing pancreatic function	Kuriyama et al[131], 2024; Vanderheiden et al[130], 2016; Fang et al[46], 2021
SGLT-2 inhibitors	Pharmacological	Increases glucose excretion through urine, reduces lipogenesis, and improves pancreatic fat deposition	Research has demonstrated that SGLT-2 inhibitors, such as dapagliflozin, effectively improve body fat distribution and reduce pancreatic fat accumulation in patients with type 2 diabetes	Ghosh et al[133], 2022; Shi et al[132], 2023
DPP-4 inhibitors	Pharmacological	Enhances insulin secretion from pancreatic beta cells, suppresses glucagon secretion from alpha cells, and improves fat accumulation	Clinical trials and animal studies indicate that the DPP-4 inhibitor sitagliptin can effectively manage pancreatic steatosis and prevent the progression of pancreatic diseases	Souza-Mello et al[128], 2010; Nag et al[127], 2024
Statins	Pharmacological	Lowers blood lipid levels, inhibits pancreatic cell proliferation, and alleviates endoplasmic reticulum stress	Animal studies have demonstrated that statins significantly reduce pancreatic fat accumulation in models subjected to high-fat diets	Chen et al[138], 2014; Krisnamurti et al[137], 2022
Angiotensin II receptor blockers	Pharmacological	Mitigates intracellular calcium overload and lipid accumulation, improving insulin sensitivity and preventing fat degeneration	Various animal studies suggest that angiotensin II receptor blockers can alleviate pancreatic steatosis by enhancing metabolic conditions in diabetic patients	Souza-Mello et al[128], 2010; Lee et al[129], 2023

GLP-1: Glucagon-like peptide-1; DDP-4: Dipeptidyl peptidase-4; SGLT-2: Sodium-glucose co-transporter type 2.