How does fatty liver form in laying hens? Lecture 4.4 explains the main causes in detail
Lecture 4.4: A discussion of the main causes of fatty liver formation in laying hens
Fatty liver has always been the most headache-inducing problem for laying hen nutritionists and farm owners, seemingly simple yet with no solution. Fatty liver not only reduces the production performance of laying hens in the mid-to-late laying period, but is also a major factor causing mortality and culling. Regardless of the nutritional status of the feed, laying hens in the mid-to-late laying period generally show varying degrees of fatty liver symptoms, which stands in sharp contrast to growing chickens and mammals. The reason for this is related to the unique protein metabolism mechanism of laying hens.
Ammonia, the end product of protein metabolism in the animal body, is toxic to the organism and must be converted and excreted as quickly as possible. To eliminate ammonia from the body, mammals excrete it by synthesizing urea (which does not consume methyl groups), while poultry mainly synthesizes uric acid in the liver and then excretes it through the kidneys. The process of uric acid synthesis in the liver is very complex. Each molecule of uric acid synthesized requires 2 molecules of active methyl groups and can simultaneously bind 4 molecules of ammonia (one of which is contained in the glycine molecule). Protein contains an average of 16% nitrogen, equivalent to 19.4% ammonia. Calculating at an average protein bioavailability of 90%, 1 kg of feed with 16% crude protein produces approximately 3.1 g of ammonia after metabolism in the body (1000g*16%*10%*19.4%=3.1g) -- all of this ammonia must be synthesized into uric acid for excretion, requiring 1.368 g of active methyl groups (3.1g/2*15/17=1.368g). If betaine provides the active methyl groups (1 molecule of betaine can provide 3 molecules of active methyl groups while also producing 1 molecule of ammonia through metabolism), then 4.27 g of pure betaine hydrochloride is needed (1.368g/3*117.15/15*120%=4.27g); if choline chloride provides the active methyl groups (1 molecule of choline chloride can provide 3 molecules of active methyl groups while also producing 1 molecule of ammonia through metabolism), then 5.09 g of pure choline chloride is needed (1.368g/3*139.63/15*120%=5.09g), or the equivalent of 10.18 g of commercial choline chloride at 50% concentration.
Methyl groups are essential for the body to synthesize methionine, choline, carnitine, creatine, phospholipids, epinephrine, RNA and DNA -- substances with important physiological functions. Folate and vitamin B12 are coenzymes of enzymes related to methyl metabolism. Whether growing or adult animals, a stable supply of methyl groups is needed. It is generally believed that animals cannot synthesize methyl groups (?) and must obtain them from food. Substances in feed that can provide active methyl groups include methionine, tryptophan, histidine, serine and glycine, as well as choline and betaine.
The above 5 amino acids including methionine each contain one active methyl group. When the body needs it or when protein is used for energy metabolism, these amino acids can serve as donors of active methyl groups. When these amino acids provide active methyl groups for uric acid synthesis, each molecule of uric acid synthesized requires 2 molecules of amino acids to provide active methyl groups while binding 4 molecules of ammonia -- of which the 2 amino acid molecules also produce 2 molecules of ammonia -- so in reality only 2 additional molecules of ammonia can be bound -- that is to say, when these amino acids provide active methyl groups for uric acid synthesis, each amino acid molecule can only eliminate 1 extra molecule of ammonia. In typical laying hen feed, the total amount of the above amino acids is about 15%, and their main role is as raw materials for protein synthesis; when the body needs it, they can also serve as active methyl group donors.
Betaine, also known as trimethylglycine (molecular formula C5H11NO2, molecular weight 117.15), is a quaternary ammonium-type alkaloid. Betaine is widely found in plants and animals, with the highest content in sugar beet molasses. Betaine can be chemically synthesized. Betaine used as a feed additive includes compound betaine at 30% and 40% concentrations and betaine hydrochloride at 98.5% concentration (the effective content calculated from the chemical formula is 75%, but the actual content is usually only about 65%). Betaine has a wide range of physiological functions: it participates in protein and lipid metabolism in the body, regulates osmotic pressure, alleviates stress, and promotes feed intake. Numerous experiments have proven that betaine, as a new type of feed additive, has broad application prospects.
As a methyl donor, betaine can promote protein synthesis. Research has found that in rats fed betaine, the betaine content in the liver increases, and as betaine content increases, betaine-homocysteine S-methyltransferase (BHMT) activity significantly rises. This enzyme is a key enzyme in the liver and kidneys for the methyl-donating metabolism of the essential amino acid methionine. BHMT can catalyze the synthesis of methionine from betaine and homocysteine. (Over 90% of the active methyl groups required for metabolism in the body are provided by methionine -- while simultaneously producing homocysteine, which is then converted back to methionine through methyl groups provided by betaine.) Betaine can promote fat metabolism and inhibit fat deposition, thereby improving lean meat percentage and carcass quality. Betaine synthesizes large amounts of carnitine through the liver, enhances fatty acid transport, promotes beta-oxidation of fatty acids within tissue cell mitochondria, provides sufficient energy for cell metabolism, and thereby reduces fat deposition.
Betaine has a buffering effect against sudden changes in osmotic pressure, maintaining cellular osmotic pressure balance. When tissue osmotic pressure changes, betaine can be absorbed by cells, preventing water loss from cells and entry of salts, enhancing the cell Na-K pump function, maintaining normal osmotic pressure in tissue cells, and regulating the balance of cellular osmotic pressure.
Adding betaine to laying hen feed has the effects of increasing the laying rate of hens, reducing the feed-to-egg ratio, and preventing fatty liver; it also reduces broken eggs and abnormal eggs; it can also improve egg quality, promote the synthesis of thick albumen and yolk, and reduce cholesterol content in the yolk.
Choline, also called trimethylethanolamine, is a raw material for synthesizing acetylcholine and lecithin, etc. It has an anti-fatty-liver effect in animals, and as a methyl donor it can also reduce the consumption of methionine and tryptophan. The choline used in feed is choline chloride, with molecular formula C5H14ClNO and molecular weight 139.63. Commercial forms include 50% powder, 60% powder, and 70% liquid. In China, the 50% powder is most commonly used, and its appearance varies depending on the carrier.
Calculated by methyl group content, 1 kg of 98.5% betaine hydrochloride is equivalent to 2.35 kg of 50% choline chloride; equivalent to 3.75 kg of 99% methionine. Methionine can directly transfer methyl groups, with the highest methyl transfer potency; betaine must first transfer its methyl groups to homocysteine to synthesize methionine, thereby indirectly providing methyl groups, and its methyl transfer potency is only 50% of methionine; choline must first be oxidized to betaine before it can provide methyl groups -- the oxidation process occurs within mitochondria, and this oxidation process requires the participation of VB12 and VB2, while being inhibited by Ni, Co, and Fe ions, so the conversion rate is not high, only 3-4%.
From this it can be seen that as an active methyl donor, betaine is the most suitable and also the most economical.
Discussion on the causes of fatty liver formation in laying hens: Fatty liver in laying hens is widespread, especially severe in the late laying period. The reason is related to the unique metabolic activities of laying hens. The different components of an egg (yolk, albumen, eggshell) are formed at different times of the day (which differs from the balanced production of growing and lactating livestock and poultry). Therefore, the body's protein synthesis metabolism is also a discontinuous process, and the daily protein requirement at different times is also uneven -- the demand for protein is high in the morning, while the demand is low in the afternoon and evening. Most of the protein digested and absorbed in the afternoon and evening is used for energy metabolism, which means that approximately 30% of the total daily feed intake contains protein that is used for energy metabolism and produces ammonia. In summary, 1 kg of feed with 16% crude protein will produce 8.69 g of ammonia after metabolism in laying hens (1000*70%*16%*10%*19.4%+1000*30%*16%*19.4%*70%=2.17+6.52=8.69).
Ammonia is toxic to the body, and eliminating ammonia toxicity is an urgent matter that must be converted and excreted as quickly as possible. About 30% can be metabolized through active methyl groups provided by amino acids containing active methyl groups such as methionine (total amount about 15%), while the remaining 70%, about 8.69 g of ammonia, requires 7.67 g of active methyl groups (8.69g*15/17=7.67g), equivalent to 19.97 g of 98.5% betaine hydrochloride (7.67g/3*117.15/15=19.97g) or 47.6 g of 50% choline chloride (7.67g/3*139.63/15*2=47.6g).
In summary, laying hens have a very large requirement for betaine and choline, and ordinary feed cannot fully meet this need. To ensure the body is protected from ammonia toxicity, laying hens prioritize synthesizing uric acid to excrete ammonia as quickly as possible. This inevitably consumes all active methyl groups in the body. Since betaine and choline are closely related to fat transport and fatty acid oxidative catabolism in the body, a deficiency of betaine and choline leads to fat metabolism disorders in the body and the formation of fatty liver.
Betaine is a raw material for synthesizing carnitine, and carnitine is the carrier for transmembrane transport of fatty acids in the body, which can promote beta-oxidation of fatty acids within tissue cell mitochondria and provide sufficient energy for cell metabolism. Due to betaine deficiency, carnitine synthesis is blocked, which leads to inhibition of fatty acid catabolism, while elevated fatty acid concentrations further promote fat synthesis.
Choline is a raw material for synthesizing lecithin, and lecithin is the carrier for fat transport in the body. Choline deficiency will affect fat transport, causing fat to accumulate in the liver and form fatty liver.
Corn-soybean meal type laying hen feed contains about 1 g of choline (equivalent to 2.68 kg of 50% choline chloride), and also contains some betaine (no data available on this), while laying hen feed generally only adds 1 kg/t of 50% choline chloride. These are far from meeting the laying hen's need for active methyl groups. Of course, the body may also synthesize some serine through glucose metabolism and transamination (this is only personal speculation), and serine can be converted to glycine. Both of these amino acids can provide active methyl groups to the body, but since the requirement is indeed too large, the rate of endogenous synthesis is far from meeting the body's metabolic needs. This may be why serine and glycine are also essential amino acids for poultry (these two amino acids are non-essential amino acids in mammals).
--------------------------------------
The data in this article are cited only for convenience in illustrating the issues, and some are merely personal speculation. The views expressed are also just one perspective, and discussion and criticism are welcome!
--------------------------------------
My observation: In high-temperature summer seasons, fatty liver is more likely to develop
--------------------------------------
I read Teacher Xie's article and gained quite a lot, thank you! Let me ask Teacher Xie another question: Regarding the use of choline and betaine in pig feed, which is better, most economical, and what are the differences? Thank you.
--------------------------------------
Teacher Xie keeps emphasizing betaine, but I still feel it is not as good as choline. From what I know, many large manufacturers only add betaine to fish feed.
--------------------------------------
Is the mechanism of fatty liver formation in broilers and laying hens the same?
--------------------------------------
If used as a methyl donor, betaine is more efficient than choline and also the most economical. I believe that for choline's own special functions, the content in ordinary feed is sufficient. As for what to use, it is more a matter of habit.
--------------------------------------
The mechanism is the same, just not as severe as in laying hens.
--------------------------------------
Pigs have a much lower requirement for active methyl groups than poultry and do not need to synthesize uric acid. I believe that methyl groups in ordinary pig feed are already sufficient (serine, glycine, and histidine can all serve as methyl donors, and pigs can synthesize serine and glycine), so adding choline chloride to pig feed may be more appropriate. However, betaine can also be converted to choline. What specifically to add can be determined according to habit. Of course, betaine does not damage the multivitamins in premixes.
--------------------------------------
As Teacher Wang said, fatty liver is more common in laying hens in summer. May I ask Teacher Xie why this is? What is the mechanism? How to avoid or alleviate it? Looking forward to your guidance!!!
--------------------------------------
Makes sense, thanks for sharing!
--------------------------------------
Based on my experience, fatty liver seems more likely to occur when soybean cake is used in the formula. I suspect it is related to Aspergillus flavus.
Ammonia, the end product of protein metabolism in the animal body, is toxic to the organism and must be converted and excreted as quickly as possible. To eliminate ammonia from the body, mammals excrete it by synthesizing urea (which does not consume methyl groups), while poultry mainly synthesizes uric acid in the liver and then excretes it through the kidneys. The process of uric acid synthesis in the liver is very complex. Each molecule of uric acid synthesized requires 2 molecules of active methyl groups and can simultaneously bind 4 molecules of ammonia (one of which is contained in the glycine molecule). Protein contains an average of 16% nitrogen, equivalent to 19.4% ammonia. Calculating at an average protein bioavailability of 90%, 1 kg of feed with 16% crude protein produces approximately 3.1 g of ammonia after metabolism in the body (1000g*16%*10%*19.4%=3.1g) -- all of this ammonia must be synthesized into uric acid for excretion, requiring 1.368 g of active methyl groups (3.1g/2*15/17=1.368g). If betaine provides the active methyl groups (1 molecule of betaine can provide 3 molecules of active methyl groups while also producing 1 molecule of ammonia through metabolism), then 4.27 g of pure betaine hydrochloride is needed (1.368g/3*117.15/15*120%=4.27g); if choline chloride provides the active methyl groups (1 molecule of choline chloride can provide 3 molecules of active methyl groups while also producing 1 molecule of ammonia through metabolism), then 5.09 g of pure choline chloride is needed (1.368g/3*139.63/15*120%=5.09g), or the equivalent of 10.18 g of commercial choline chloride at 50% concentration.
Methyl groups are essential for the body to synthesize methionine, choline, carnitine, creatine, phospholipids, epinephrine, RNA and DNA -- substances with important physiological functions. Folate and vitamin B12 are coenzymes of enzymes related to methyl metabolism. Whether growing or adult animals, a stable supply of methyl groups is needed. It is generally believed that animals cannot synthesize methyl groups (?) and must obtain them from food. Substances in feed that can provide active methyl groups include methionine, tryptophan, histidine, serine and glycine, as well as choline and betaine.
The above 5 amino acids including methionine each contain one active methyl group. When the body needs it or when protein is used for energy metabolism, these amino acids can serve as donors of active methyl groups. When these amino acids provide active methyl groups for uric acid synthesis, each molecule of uric acid synthesized requires 2 molecules of amino acids to provide active methyl groups while binding 4 molecules of ammonia -- of which the 2 amino acid molecules also produce 2 molecules of ammonia -- so in reality only 2 additional molecules of ammonia can be bound -- that is to say, when these amino acids provide active methyl groups for uric acid synthesis, each amino acid molecule can only eliminate 1 extra molecule of ammonia. In typical laying hen feed, the total amount of the above amino acids is about 15%, and their main role is as raw materials for protein synthesis; when the body needs it, they can also serve as active methyl group donors.
Betaine, also known as trimethylglycine (molecular formula C5H11NO2, molecular weight 117.15), is a quaternary ammonium-type alkaloid. Betaine is widely found in plants and animals, with the highest content in sugar beet molasses. Betaine can be chemically synthesized. Betaine used as a feed additive includes compound betaine at 30% and 40% concentrations and betaine hydrochloride at 98.5% concentration (the effective content calculated from the chemical formula is 75%, but the actual content is usually only about 65%). Betaine has a wide range of physiological functions: it participates in protein and lipid metabolism in the body, regulates osmotic pressure, alleviates stress, and promotes feed intake. Numerous experiments have proven that betaine, as a new type of feed additive, has broad application prospects.
As a methyl donor, betaine can promote protein synthesis. Research has found that in rats fed betaine, the betaine content in the liver increases, and as betaine content increases, betaine-homocysteine S-methyltransferase (BHMT) activity significantly rises. This enzyme is a key enzyme in the liver and kidneys for the methyl-donating metabolism of the essential amino acid methionine. BHMT can catalyze the synthesis of methionine from betaine and homocysteine. (Over 90% of the active methyl groups required for metabolism in the body are provided by methionine -- while simultaneously producing homocysteine, which is then converted back to methionine through methyl groups provided by betaine.) Betaine can promote fat metabolism and inhibit fat deposition, thereby improving lean meat percentage and carcass quality. Betaine synthesizes large amounts of carnitine through the liver, enhances fatty acid transport, promotes beta-oxidation of fatty acids within tissue cell mitochondria, provides sufficient energy for cell metabolism, and thereby reduces fat deposition.
Betaine has a buffering effect against sudden changes in osmotic pressure, maintaining cellular osmotic pressure balance. When tissue osmotic pressure changes, betaine can be absorbed by cells, preventing water loss from cells and entry of salts, enhancing the cell Na-K pump function, maintaining normal osmotic pressure in tissue cells, and regulating the balance of cellular osmotic pressure.
Adding betaine to laying hen feed has the effects of increasing the laying rate of hens, reducing the feed-to-egg ratio, and preventing fatty liver; it also reduces broken eggs and abnormal eggs; it can also improve egg quality, promote the synthesis of thick albumen and yolk, and reduce cholesterol content in the yolk.
Choline, also called trimethylethanolamine, is a raw material for synthesizing acetylcholine and lecithin, etc. It has an anti-fatty-liver effect in animals, and as a methyl donor it can also reduce the consumption of methionine and tryptophan. The choline used in feed is choline chloride, with molecular formula C5H14ClNO and molecular weight 139.63. Commercial forms include 50% powder, 60% powder, and 70% liquid. In China, the 50% powder is most commonly used, and its appearance varies depending on the carrier.
Calculated by methyl group content, 1 kg of 98.5% betaine hydrochloride is equivalent to 2.35 kg of 50% choline chloride; equivalent to 3.75 kg of 99% methionine. Methionine can directly transfer methyl groups, with the highest methyl transfer potency; betaine must first transfer its methyl groups to homocysteine to synthesize methionine, thereby indirectly providing methyl groups, and its methyl transfer potency is only 50% of methionine; choline must first be oxidized to betaine before it can provide methyl groups -- the oxidation process occurs within mitochondria, and this oxidation process requires the participation of VB12 and VB2, while being inhibited by Ni, Co, and Fe ions, so the conversion rate is not high, only 3-4%.
From this it can be seen that as an active methyl donor, betaine is the most suitable and also the most economical.
Discussion on the causes of fatty liver formation in laying hens: Fatty liver in laying hens is widespread, especially severe in the late laying period. The reason is related to the unique metabolic activities of laying hens. The different components of an egg (yolk, albumen, eggshell) are formed at different times of the day (which differs from the balanced production of growing and lactating livestock and poultry). Therefore, the body's protein synthesis metabolism is also a discontinuous process, and the daily protein requirement at different times is also uneven -- the demand for protein is high in the morning, while the demand is low in the afternoon and evening. Most of the protein digested and absorbed in the afternoon and evening is used for energy metabolism, which means that approximately 30% of the total daily feed intake contains protein that is used for energy metabolism and produces ammonia. In summary, 1 kg of feed with 16% crude protein will produce 8.69 g of ammonia after metabolism in laying hens (1000*70%*16%*10%*19.4%+1000*30%*16%*19.4%*70%=2.17+6.52=8.69).
Ammonia is toxic to the body, and eliminating ammonia toxicity is an urgent matter that must be converted and excreted as quickly as possible. About 30% can be metabolized through active methyl groups provided by amino acids containing active methyl groups such as methionine (total amount about 15%), while the remaining 70%, about 8.69 g of ammonia, requires 7.67 g of active methyl groups (8.69g*15/17=7.67g), equivalent to 19.97 g of 98.5% betaine hydrochloride (7.67g/3*117.15/15=19.97g) or 47.6 g of 50% choline chloride (7.67g/3*139.63/15*2=47.6g).
In summary, laying hens have a very large requirement for betaine and choline, and ordinary feed cannot fully meet this need. To ensure the body is protected from ammonia toxicity, laying hens prioritize synthesizing uric acid to excrete ammonia as quickly as possible. This inevitably consumes all active methyl groups in the body. Since betaine and choline are closely related to fat transport and fatty acid oxidative catabolism in the body, a deficiency of betaine and choline leads to fat metabolism disorders in the body and the formation of fatty liver.
Betaine is a raw material for synthesizing carnitine, and carnitine is the carrier for transmembrane transport of fatty acids in the body, which can promote beta-oxidation of fatty acids within tissue cell mitochondria and provide sufficient energy for cell metabolism. Due to betaine deficiency, carnitine synthesis is blocked, which leads to inhibition of fatty acid catabolism, while elevated fatty acid concentrations further promote fat synthesis.
Choline is a raw material for synthesizing lecithin, and lecithin is the carrier for fat transport in the body. Choline deficiency will affect fat transport, causing fat to accumulate in the liver and form fatty liver.
Corn-soybean meal type laying hen feed contains about 1 g of choline (equivalent to 2.68 kg of 50% choline chloride), and also contains some betaine (no data available on this), while laying hen feed generally only adds 1 kg/t of 50% choline chloride. These are far from meeting the laying hen's need for active methyl groups. Of course, the body may also synthesize some serine through glucose metabolism and transamination (this is only personal speculation), and serine can be converted to glycine. Both of these amino acids can provide active methyl groups to the body, but since the requirement is indeed too large, the rate of endogenous synthesis is far from meeting the body's metabolic needs. This may be why serine and glycine are also essential amino acids for poultry (these two amino acids are non-essential amino acids in mammals).
--------------------------------------
The data in this article are cited only for convenience in illustrating the issues, and some are merely personal speculation. The views expressed are also just one perspective, and discussion and criticism are welcome!
--------------------------------------
My observation: In high-temperature summer seasons, fatty liver is more likely to develop
--------------------------------------
I read Teacher Xie's article and gained quite a lot, thank you! Let me ask Teacher Xie another question: Regarding the use of choline and betaine in pig feed, which is better, most economical, and what are the differences? Thank you.
--------------------------------------
Teacher Xie keeps emphasizing betaine, but I still feel it is not as good as choline. From what I know, many large manufacturers only add betaine to fish feed.
--------------------------------------
Is the mechanism of fatty liver formation in broilers and laying hens the same?
--------------------------------------
If used as a methyl donor, betaine is more efficient than choline and also the most economical. I believe that for choline's own special functions, the content in ordinary feed is sufficient. As for what to use, it is more a matter of habit.
--------------------------------------
The mechanism is the same, just not as severe as in laying hens.
--------------------------------------
Pigs have a much lower requirement for active methyl groups than poultry and do not need to synthesize uric acid. I believe that methyl groups in ordinary pig feed are already sufficient (serine, glycine, and histidine can all serve as methyl donors, and pigs can synthesize serine and glycine), so adding choline chloride to pig feed may be more appropriate. However, betaine can also be converted to choline. What specifically to add can be determined according to habit. Of course, betaine does not damage the multivitamins in premixes.
--------------------------------------
As Teacher Wang said, fatty liver is more common in laying hens in summer. May I ask Teacher Xie why this is? What is the mechanism? How to avoid or alleviate it? Looking forward to your guidance!!!
--------------------------------------
Makes sense, thanks for sharing!
--------------------------------------
Based on my experience, fatty liver seems more likely to occur when soybean cake is used in the formula. I suspect it is related to Aspergillus flavus.