Dietary soy protein reverses obesity-induced liver steatosis and alters fecal microbial composition independent of isoflavone level

Authors: HAKKAK, REZA - University Arkansas For Medical Sciences (UAMS); KOROURIAN, SOHEILA - University Arkansas For Medical Sciences (UAMS); LI, WEI - University Arkansas For Medical Sciences (UAMS); SPRAY, BEVERLY - Arkansas Children'S Hospital; TWADDLE, NATHAN - Food And Drug Administration(FDA); RANDOLPH, CHRISTOPHER - University Arkansas For Medical Sciences (UAMS); BØRSHEIM, ELISABET - Arkansas Children'S Nutrition Research Center (ACNC); ROBESON - University Arkansas For Medical Sciences (UAMS)

Submitted to: Frontiers in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/9/2024
Publication Date: 10/28/2024
Citation: Hakkak, R., Korourian, S., Li, W., Spray, B., Twaddle, N., Randolph, C., Børsheim, E., Robeson, .S. 2024. Dietary soy protein reverses obesity-induced liver steatosis and alters fecal microbial composition independent of isoflavone level. Frontiers in Nutrition. 11(2024):1487859. https://doi.org/10.3389/fnut.2024.1487859.
DOI: https://doi.org/10.3389/fnut.2024.1487859

Interpretive Summary: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health issue linked to the rise in obesity. Changes in diet can help reduce the effects of MASLD, partly by improving gut bacteria. In earlier research, soy protein concentrate (SPC), either low or high in isoflavones (natural plant compounds), helped prevent liver fat buildup in young obese rats. This new study looked at whMetabolic dysfunction-associated steatotic liver disease (MASLD) is a serious health issue linked to the rise in obesity. Changes in diet can help reduce the effects of MASLD, partly by improving gut bacteria. In earlier research, soy protein concentrate (SPC), either low or high in isoflavones (natural plant compounds), helped prevent liver fat buildup in young obese rats. This new study looked at whether SPC with low (LIF) or high (HIF) isoflavone levels could reverse liver fat in adult obese rats that already had liver damage, and if it would affect their gut bacteria. After 8 weeks on a regular casein (CAS) diet, rats were switched to CAS, SPC-LIF, or SPC-HIF diets for 10 weeks. Both SPC diets reduced liver fat and liver weight compared to the CAS diet, but didn't change body weight or certain blood markers. The rats on the high-isoflavone diet (SPC-HIF) had an even greater drop in liver weight and higher levels of certain beneficial compounds. While the types of gut bacteria changed in the SPC groups, the overall diversity of gut bacteria stayed the same. In summary, soy protein helped reduce liver fat in obese rats, and this was linked to changes in their gut bacteria.could reverse liver fat in adult obese rats that already had liver damage, and if it would affect their gut bacteria. After 8 weeks on a regular casein (CAS) diet, rats were switched to CAS, SPC-LIF, or SPC-HIF diets for 10 weeks. Both SPC diets reduced liver fat and liver weight compared to the CAS diet, but didn't change body weight or certain blood markers. The rats on the high-isoflavone diet (SPC-HIF) had an even greater drop in liver weight and higher levels of certain beneficial compounds. While the types of gut bacteria changed in the SPC groups, the overall diversity of gut bacteria stayed the same. In summary, soy protein helped reduce liver fat in obese rats, and this was linked to changes in their gut bacteria.

Technical Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern that is exacerbated by the obesity pandemic. Dietary interventions have the potential to alleviate obesity-associated MASLD through variable mechanisms, including optimizing the gut microbiota. Previously, we reported that soy protein concentrate (SPC) with low or high levels of isoflavone (LIF or HIF) protected young obese Zucker rats from developing liver steatosis. The current study was designed to test whether SPC-LIF and SPC-HIF diets would reverse liver steatosis and alter fecal microbial composition in adult obese Zucker rats with existing steatosis. Six-week-old male obese Zucker rats (n = 2826) were fed a casein control diet (CAS) for 8 weeks and 7 rats were randomly selected and sacrificed to confirm liver steatosis. The remaining rats were randomly assigned to receive CAS, SPC-LIF, or SPC-HIF diet (n = 6 -7/group) for an additional 10 weeks. Compared to CAS diet, feeding SPC-LIF and SPC-HIF diets resulted in significantly lower liver weight, liver steatosis score, and liver microvesicular score (p < 0.05), but did not lead to difference in body weight, liver macrovesicular score, serum ALT, or serum AST. Isoflavone levels (e.g. LIF vs. HIF) did not affect any of these measurements except in the SPC-HIF group, which had an additional decrease in liver weight (p < 0.05) compared to the SPC-LIF group. The SPC-HIF group also had significantly higher levels of the glycone forms of daidzein, genistein, and equol as well as the total levels of daidzein, genistein, and equol compared to SPC-LIF or CAS diet fed rats (p < 0.05). The distribution of microbial communities based on measures of beta diversity of both SPC-LIF and SPC-HIF groups were significantly different to that of the CAS group (p = 0.005). Conversely, Alpha-diversity did not differ between any of the groups. When taken together, dietary soy protein can reverse liver steatosis in adult Zucker rats, and the reversal of steatosis is accompanied by alterations in gut microbial composition.