Soybean oil causes genetic changes in the brain

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New UC Riverside research shows soybean oil not only leads to obesity and diabetes, but could also affect neurological conditions like autism, Alzheimer’s disease, anxiety, and depression.

Used for fast food frying, added to packaged foods, and fed to livestock, soybean oil is by far the most widely produced and consumed edible oil in the U.S., according to the U.S. Department of Agriculture. In all likelihood, it is not healthy for humans.

It certainly is not good for mice. The new study, published this month in the journal Endocrinology, compared mice fed three different diets high in fat: soybean oil, soybean oil modified to be low in linoleic acid, and coconut oil.

The same UCR research team found in 2015 that soybean oil induces obesity, diabetes, insulin resistance, and fatty liver in mice. Then in a 2017 study, the same group learned that if soybean oil is engineered to be low in linoleic acid, it induces less obesity and insulin resistance.

However, in the study released this month, researchers did not find any difference between the modified and unmodified soybean oil’s effects on the brain. Specifically, the scientists found pronounced effects of the oil on the hypothalamus, where a number of critical processes take place.

“The hypothalamus regulates body weight via your metabolism, maintains body temperature, is critical for reproduction and physical growth as well as your response to stress,” said Margarita Curras-Collazo, a UCR associate professor of neuroscience and lead author on the study.

The team determined a number of genes in mice fed soybean oil were not functioning correctly. One such gene produces the “love” hormone, oxytocin. In soybean oil-fed mice, levels of oxytocin in the hypothalamus went down.

The research team discovered roughly 100 other genes also affected by the soybean oil diet. They believe this discovery could have ramifications not just for energy metabolism, but also for proper brain function and diseases such as autism or Parkinson’s disease.

However, it is important to note there is no proof the oil causes these diseases.

Additionally, the team notes the findings only apply to soybean oil — not to other soy products or to other vegetable oils.

Identifying the compounds responsible for the negative effects is an important area for the team’s future research.

“Do not throw out your tofu, soymilk, edamame, or soy sauce,” said Frances Sladek, a UCR toxicologist and professor of cell biology.

“Many soy products only contain small amounts of the oil, and large amounts of healthful compounds such as essential fatty acids and proteins.”

A caveat for readers concerned about their most recent meal is that this study was conducted on mice, and mouse studies do not always translate to the same results in humans.

Also, this study utilized male mice. Because oxytocin is so important for maternal health and promotes mother-child bonding, similar studies need to be performed using female mice.

One additional note on this study — the research team has not yet isolated which chemicals in the oil are responsible for the changes they found in the hypothalamus.

But they have ruled out two candidates. It is not linoleic acid, since the modified oil also produced genetic disruptions; nor is it stigmasterol, a cholesterol-like chemical found naturally in soybean oil.

Identifying the compounds responsible for the negative effects is an important area for the team’s future research.

“This could help design healthier dietary oils in the future,” said Poonamjot Deol, an assistant project scientist in Sladek’s laboratory and first author on the study.

“The dogma is that saturated fat is bad and unsaturated fat is good. Soybean oil is a polyunsaturated fat, but the idea that it’s good for you is just not proven,” Sladek said.

Indeed, coconut oil, which contains saturated fats, produced very few changes in the hypothalamic genes.

“If there’s one message I want people to take away, it’s this: reduce consumption of soybean oil,” Deol said about the most recent study.


Sterility is a common phenomenon among plants. On the basis of the mode of inheritance, two main types of sterility have been identified in plants: cytoplasmic sterility and nucleus-dependent sterility (Zhang et al., 2008Chen and Liu, 2014Yang et al., 2014Speth et al., 2015Bohra et al., 2016Chang et al., 2016Liu et al., 2018Xie et al., 2018).

In plant breeding, hybrid seeds/lines are advantageous because they produce high yields. In comparison to female sterility, male sterility, including cytoplasmic male sterility (CMS) and genetic male sterility (GMS), has wide applications in commercial crop hybrids because male sterility greatly increases the effectiveness of F1 hybrid seed production without manual pollination and can dramatically reduce production costs (Cheng et al., 2007Xu et al., 2007Chen et al., 2011Huang et al., 2014).

The most successful application of male sterility in crop hybrid seed production is in rice (Oryza sativaCheng et al., 2007Huang et al., 2014). In recent years, many male sterility genes have been identified and cloned, and the underlying genetic and molecular mechanisms have been described.

For example, MS1, a newly evolved gene in wheat (Triticum aestivum; Poaceae), is specifically expressed in microsporocytes and is essential for microgametogenesis (Wang et al., 2017). OsPKS2 encodes a polyketide synthase that is involved in pollen wall formation in rice. Male sterility can be caused by OsPKS2 mutation (Zou et al., 2018).

Two-line hybrid rice was developed based on the discovery of photoperiod-sensitive male sterility (PSMS) germplasm, which is male-sterile under long-day conditions but fertile under short-day conditions (Fan et al., 2016).

Recently, the molecular mechanism of a PSMS gene, Pms1, which encodes a long-non-coding RNA, PMS1T, was elucidated (Fan et al., 2016). In addition, other male-sterility genes, such as ZmMs33 in maize (Zea maysXie et al., 2018) and MSH1 in Brassica juncea (Zhao et al., 2016), have been cloned and well characterized.

Soybean is an economically important crop that is grown worldwide for the high contents of oil (20–25%) and protein (42–45%) in its seeds (Adak and Kibritci, 2016). Although soybean is extremely important for human consumption, it has a lower yield than other important food crops, such as wheat, rice, and maize (Wen et al., 2016Gao et al., 2018Ma et al., 2018).

Although a three-line system based on CMS has been developed in soybean, large-scale hybrid seed production is difficult to achieve because of the extremely low frequency of natural cross-pollination (Ray et al., 2003).

Therefore, the application of male sterility in soybean hybrid seed-production research has typically lagged behind other crops. At least three CMS restorer loci have been identified in soybean (Wang et al., 2016).

The CMS restorer locus Rf-m was fine-mapped to chromosome 16 between the flanking markers GmSSR1602 and GmSSR1610 with genetic distances of 0.11 and 0.2502 cM, respectively, and a pentatricopeptide repeat gene was predicted to be the candidate restorer gene. Yang et al. (2010) mapped two independent Rf loci linked to Satt626 in molecular linkage group (MLG) M and Satt300 in MLG A1 at genetic distances of 9.75 and 11.18 cM, respectively. With regard to GMS, more than 20 male-sterility loci have been reported, including ms1ms9msMOSmspst1st8ASR-7-206A03-2137A05-133A06-204, and st_A06-2/6 (Owen, 1928Hadley and Starnes, 1964Palmer, 19742000Palmer et al., 19782008Delannay and Palmer, 1982Palmer and Kaul, 1983Graybosch and Palmer, 19851988Graybosch et al., 1987Horner and Palmer, 1995Jin et al., 19971998Palmer and Horner, 2000Cervantes-Martinez et al., 20072009Rebeccaa et al., 2011Baumbach et al., 2012), the majority of which have been mapped to a linkage group (Yang et al., 2014Speth et al., 2015). However, none of these loci have been successfully cloned or fine-mapped. Therefore, the molecular mechanisms of male sterility in soybean are largely unknown.

In this study, we identified a soybean male-sterile mutant line from a soybean breeding line. We investigated the genetic mechanism of the mutant line and fine-mapped the locus for male sterility. Our results provide a foundation for cloning male-sterility genes and elucidating the molecular mechanism of male sterility in soybean.

Results

Phenotypic Characterization of Pollen Grains From Sterile and Fertile Plants

The growth and development of the sterile line (St-M) and the fertile wild-type parent (F-wt) were compared over an entire growing season. No difference in phenotype between St-M and F-wt was observed before flowering.

From the R1 growth stage, St-M plants showed early abscission of flowers or development of small, fleshy but seedless pods (Figure 1b), whereas F-wt plants showed normal flower and fruit development (Figure 1a).

Observation of about 3400 St-M sterile plants showed that sterility was absolute with no seed development observed. Given that St-M plants could produce small pods, we speculated that the sterility of St-M was not caused by the pistil, but rather by abnormal pollen development.

To test this hypothesis, we observed pollen grains microscopically. The pollen grains from St-M plants varied greatly in size and stained poorly with I2KI, whereas pollen grains from F-wt plants were uniform in size and were stained intensely with I2KI (Figures 1e,f).

These observations indicated that the St-M pollen grains were aborted. Observation of pollens grains from St-M and F-wt with a SEM showed that F-wt produced small, rounded pollen grains full of cytoplasm, whereas St-M pollens grains were shriveled or collapsed (Figures 1c,d).

In a previous study, cytological analysis suggested that male sterility in ms1 soybean was caused by the failure of cytokinesis after telophase II of meiosis (Albertsen and Palmer, 1979). Lipids and starch were deposited in the enlarged but non-functional pollen grains (Albertsen and Palmer, 1979).

To determine whether the mst-M gene was involved in similar process, the number and diameter of pollen grains in F-wt and St-M plants were evaluated.

The results showed that the average total number of pollen grains per F-wt flower was about 580, whereas St-M flowers (150) had about one-quarter the pollen grains of F-wt (Figure 2A). The average diameter of St-M pollen grains was about 36 μm, which was approximately 1.6-fold greater than that of F-wt pollen grains (Figure 2B). We concluded that the sterility of St-M was caused by abortion of the pollen grains.


Source:
UCR

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