Fat accumulation outside subcutaneous adipose tissue often has unfavourable effects on systemic metabolism. In addition to non-alcoholic fatty liver disease, which has received considerable attention, pancreatic fat has become an important area of research throughout the past 10 years. While a number of diagnostic approaches are available to quantify pancreatic fat, multi-echo Dixon MRI is currently the most developed method. Initial studies have shown associations between pancreatic fat and the metabolic syndrome, impaired glucose metabolism and type 2 diabetes mellitus. Pancreatic fat is linked to reduced insulin secretion, at least under specific circumstances such as prediabetes, low BMI and increased genetic risk of type 2 diabetes mellitus. This Review summarizes the possible causes and metabolic consequences of pancreatic fat accumulation. In addition, potential therapeutic approaches for addressing pancreatic fat accumulation are discussed.
A number of studies have demonstrated a link between pancreatic fat and impaired glucose metabolism, as well as between pancreatic fat and type 2 diabetes mellitus.
Possible causes of pancreatic steatosis include the metabolic syndrome, non-alcoholic fatty liver disease, alcohol consumption and specific genetic diseases.
Chronic accumulation of fat in the pancreas can lead to chronic pancreatitis, pancreatic neoplasia, disturbed glucose metabolism and impaired insulin secretion.
Different approaches, such as a hypocaloric diet, exercise, bariatric surgery and pharmacological interventions, can reduce pancreatic fat content.
Preliminary evidence shows that a reduction in pancreatic fat improves insulin metabolism, but further experimental evidence is needed to untangle the underlying mechanisms.
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We thank S. Hülskämper (University of Tübingen) for artistic support in preparation of the first drafts of the figures. The authors acknowledge support (grant no. 01GI0925) from the Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD). The authors also acknowledge the support from JSPS KAKENHI (grant no. 19K16978).
Since January 2020, B.A.J. has been an employee and shareholder of Eli Lilly and Company. Outside the current work, R.W. reports lecture fees from Novo Nordisk and Sanofi, and travel grants from Eli Lilly. R.W. served on an advisory board for Akcea Therapeutics and Daiichi Sankyo. In addition to his current work, A.L.B. reports lecture fees from AstraZeneca, Boehringer Ingelheim and Novo Nordisk. A.L.B. served on advisory boards for AstraZeneca, Boehringer Ingelheim and Novo Nordisk. Besides his current work, A.F. reports lecture fees from and advisory board membership for Sanofi, Novo Nordisk, Eli Lilly and AstraZeneca. In addition to his current work, M.H. reports research grants from Boehringer Ingelheim and Sanofi (both to the University Hospital of Tübingen) and lecture fees from Sanofi, Novo Nordisk, Boehringer Ingelheim, Eli Lilly and Merck Sharp & Dohme. He also served on an advisory board for Boehringer Ingelheim. The other authors declare no competing interests.
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The ability of a surface to reflect ultrasound in ultrasonography.
The radiological absorption of X-rays.
- Hounsfield units
(HU). Units for quantitatively describing the radiodensity of different body tissues and materials, standardized in relation to the attenuation coefficients of air (−1,000 HU) and distilled water (0 HU), named after the developer of CT, Sir Godfrey Hounsfield.
- Dixon method
An MR imaging technique that enables separation of fat and water by the inherent chemical shift difference of protons bound to lean tissues and lipids, named after the American physicist and developer W. Thomas Dixon.
- Proton density fat fraction
The proton density fat fraction is a non-invasive and accurate measure of the percentage of fat infiltration in organs calculated from multi-echo Dixon images.
An effective transverse relaxation time resulting from the inherent transverse relaxation time T2 and microscopic magnetic field inhomogenities in MR gradient echo images.
A unit of magnetic field strength. Typical clinical MR scanners work with field strengths between 1.5 T and 3 T.
Describes the relationship between the measured signal and concentration/amount of the assessed substance, e.g. amount of lipids within the pancreas.
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Cite this article
Wagner, R., Eckstein, S.S., Yamazaki, H. et al. Metabolic implications of pancreatic fat accumulation. Nat Rev Endocrinol 18, 43–54 (2022). https://doi.org/10.1038/s41574-021-00573-3
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