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Why Fat Would Accumulate In The Pancreas Causing Fatty Pancreas?
Question: An academic question.
I am interested in understanding why fat would accumulate in the pancreas that some people develop fatty pancreas. Is there a known cause? I can't find anywhere on the net that talks about causes in this case. I can understand that the liver might get fatty if it is involved in other jobs and maybe stores fats/ triglycerides after digestion temporarily and then never gets to move them, eg if the person is alcoholic or diabetic. But I can't see the logic why fat would be stored in the pancreas. .
I am interested in understanding why fat would accumulate in the pancreas that some people develop fatty pancreas. Is there a known cause? I can't find anywhere on the net that talks about causes in this case. I can understand that the liver might get fatty if it is involved in other jobs and maybe stores fats/ triglycerides after digestion temporarily and then never gets to move them, eg if the person is alcoholic or diabetic. But I can't see the logic why fat would be stored in the pancreas. .
Brief Answer:
This is due to increased exposure of NEFA and TG
Detailed Answer:
Hi XXXXXXX,
Welcome to HCM. Thanks for posting the question.
Similar to NAFLD (non alcoholic fatty liver disease - Fatty liver) there is NAFPD (Non alcoholic fatty pancreatic disease). This is less recognised because fatty liver can be easily recognised in ultrasound abdomen while pancreatic fat is difficult to detect because it is a posterior structure.
The possible explanations of fat accumulation in pancreas:
Increased accumulation of NEFA (non esterified fatty acid) in pancreas. This increased NEFA can be due to increased lipolysis in adipocytes in obesity or due to increased liver out put of triglyceride rich particles due to insulin resistance.
When the amount of NEFA exceeds the utilisation in pancreas, this leads to accumulation of fat in pancreas. This leads to a condition called "lipotoxicity" resulting in decreased beta-cell function. The triglyceride accumulation in pancreas is worsened by high blood sugars.
Hope I have answered your question. If you have any further questions I will be happy to help.
Regards
Dr Ajish TP
Consultant Endocrinologist
This is due to increased exposure of NEFA and TG
Detailed Answer:
Hi XXXXXXX,
Welcome to HCM. Thanks for posting the question.
Similar to NAFLD (non alcoholic fatty liver disease - Fatty liver) there is NAFPD (Non alcoholic fatty pancreatic disease). This is less recognised because fatty liver can be easily recognised in ultrasound abdomen while pancreatic fat is difficult to detect because it is a posterior structure.
The possible explanations of fat accumulation in pancreas:
Increased accumulation of NEFA (non esterified fatty acid) in pancreas. This increased NEFA can be due to increased lipolysis in adipocytes in obesity or due to increased liver out put of triglyceride rich particles due to insulin resistance.
When the amount of NEFA exceeds the utilisation in pancreas, this leads to accumulation of fat in pancreas. This leads to a condition called "lipotoxicity" resulting in decreased beta-cell function. The triglyceride accumulation in pancreas is worsened by high blood sugars.
Hope I have answered your question. If you have any further questions I will be happy to help.
Regards
Dr Ajish TP
Consultant Endocrinologist
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Thank you for your answer.
You raise some matters that are interesting to me.
You say that the lipotoxicity results in decreased beta-cell function.
Lipid bodies are used for membrane repair and maintenance so is it possible that beta cells are in the early stages of being attacked by the immune system and that they are involved in undergoing repairs and that is why they take up the extra lipids?
Also is it possible that while they are trying to repair they may not be involved in making or releasing insulin?
Also you say that the triglyceride accumulation is worsened by high blood sugars. Is it possible that the high blood sugars are due to stress and inflammation and that would explain the immune system doing damage in the area.
I have found that if a person is covertly threatened and they are at the same time presented with ideas about harm or damage and they don't realize that the ideas are only suggestions, they may react so that their immune system begins an inflammatory response in the area indicated by the ideas. I have reversed reactions, especially allergies and cancer simply by recognizing the ideas are false. And in the case of allergies I have seen very quick healing, within half an hour, even though the fear reaction is still ongoing owing to the danger posed, hence there are still high blood sugars but on realizing that the danger is external and not in the body, the erroneous reaction of the immune system ceases.
Thanks
XXXXXXX
You raise some matters that are interesting to me.
You say that the lipotoxicity results in decreased beta-cell function.
Lipid bodies are used for membrane repair and maintenance so is it possible that beta cells are in the early stages of being attacked by the immune system and that they are involved in undergoing repairs and that is why they take up the extra lipids?
Also is it possible that while they are trying to repair they may not be involved in making or releasing insulin?
Also you say that the triglyceride accumulation is worsened by high blood sugars. Is it possible that the high blood sugars are due to stress and inflammation and that would explain the immune system doing damage in the area.
I have found that if a person is covertly threatened and they are at the same time presented with ideas about harm or damage and they don't realize that the ideas are only suggestions, they may react so that their immune system begins an inflammatory response in the area indicated by the ideas. I have reversed reactions, especially allergies and cancer simply by recognizing the ideas are false. And in the case of allergies I have seen very quick healing, within half an hour, even though the fear reaction is still ongoing owing to the danger posed, hence there are still high blood sugars but on realizing that the danger is external and not in the body, the erroneous reaction of the immune system ceases.
Thanks
XXXXXXX
Brief Answer:
See detailed answer
Detailed Answer:
Hi XXXXXXX,
Welcome back, good day.
The exact mechanism of lipotoxicity is not clearly understood. Long chain fatty acyl co A(LC-CoA) is one metabolite which is postulated to have deleterious effect in pancreatic cells. Fatty acids are essential fuels even in beta cells, but when present in excess over long periods leads to decreased insulin gene expression and beta cell death.
In type 2 diabetes these mechanisms are multi factorial. The oxidative stress and free radicals are more responsible for beta cell damage in type 2 diabetes than immune mechanisms, though the immune theory is also well established in type 2 diabetes. That is the reason why some type 2 diabetes behave like type 1 and become insulin dependent.
Probably as you have explained when the beta cells are damaged, their focus should be on survival, rather than insulin production.
High glucose levels leads to accumulation of citrate in cells, which will inhibit an enzyme carnitine-palmitoyl-tranferase-1, which is responsible for transport of fatty acid to mitochondria for metabolism. This will result in accumulation of fatty acid in cytoplasm. This is again the best postulated explanation of increased glucose leading to lipid accumulation.
Hope this will clear some of your doubts
Regards
Dr Ajish TP
See detailed answer
Detailed Answer:
Hi XXXXXXX,
Welcome back, good day.
The exact mechanism of lipotoxicity is not clearly understood. Long chain fatty acyl co A(LC-CoA) is one metabolite which is postulated to have deleterious effect in pancreatic cells. Fatty acids are essential fuels even in beta cells, but when present in excess over long periods leads to decreased insulin gene expression and beta cell death.
In type 2 diabetes these mechanisms are multi factorial. The oxidative stress and free radicals are more responsible for beta cell damage in type 2 diabetes than immune mechanisms, though the immune theory is also well established in type 2 diabetes. That is the reason why some type 2 diabetes behave like type 1 and become insulin dependent.
Probably as you have explained when the beta cells are damaged, their focus should be on survival, rather than insulin production.
High glucose levels leads to accumulation of citrate in cells, which will inhibit an enzyme carnitine-palmitoyl-tranferase-1, which is responsible for transport of fatty acid to mitochondria for metabolism. This will result in accumulation of fatty acid in cytoplasm. This is again the best postulated explanation of increased glucose leading to lipid accumulation.
Hope this will clear some of your doubts
Regards
Dr Ajish TP
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Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
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