Rapeseed (canola) oil aggravates metabolic syndrome-like conditions in male but not in female stroke-prone spontaneously hypertensive rats (SHRSP)

Mai Nishikawa; Naoki Ohara; Yukiko Naito; Yoshiaki Saito; Chihiro Amma; Kenjiro Tatematsu; Jinhua Baoyindugurong; Daisuke Miyazawa; Yoko Hashimoto; Harumi Okuyama

doi:10.1016/j.toxrep.2022.01.011

Rapeseed (canola) oil aggravates metabolic syndrome-like conditions in male but not in female stroke-prone spontaneously hypertensive rats (SHRSP)

Toxicol Rep. 2022 Feb 7:9:256-268. doi: 10.1016/j.toxrep.2022.01.011. eCollection 2022.

Authors

Affiliations

¹ College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi 463-8521, Japan.
² School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0373, Japan.
³ Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano, Kanagawa 257-8523, Japan.
⁴ Gifu Pharmaceutical University, 5-6-1 Mitabora, Gifu, Gifu 502-8585, Japan.
⁵ Inner Mongolia Agricultural University, College of Food Science and Engineering, Zhaowuda Rd. 306, Hohhot, Inner Mongolia 010018, PR China.
⁶ School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.

Abstract

This study was conducted to investigate whether or not there are sex differences in canola oil (CAN)-induced adverse events in the rat and to understand the involvement and the role of testosterone in those events, including life-shortening. Stroke-prone spontaneously hypertensive rats (SHRSP) of both sexes were fed a diet containing 10 wt/wt% soybean oil (SOY, control) or CAN as the sole dietary fat. The survival of the males fed the CAN diet was significantly shorter than that of those fed the SOY diet. In contrast, the survival of the females was not affected by CAN. The males fed the CAN diet showed elevated blood pressure, thrombopenia and insulin-tolerance, which are major symptoms of metabolic syndrome, whereas such changes by the CAN diet were not found in the females. Plasma testosterone was significantly lower in animals of both sexes fed the CAN diet than in those fed the SOY diet, but interestingly, the lowered testosterone was accompanied by a marked increase in plasma aldosterone only in the males. These results demonstrate significant sex differences in CAN-toxicity and suggest that those sex differences may be attributable to the increased aldosterone level, which triggers aggravation of the genetic diseases specific to SHRSP, that is, metabolic syndrome-like conditions, but only in the males. The present results also suggest that testosterone may negatively regulate aldosterone production in the physiology of the males, and the inhibition of that negative regulation caused by the CAN diet is one of the possible causes of the adverse events.

Keywords: AUC, area under the curve; Aldosterone; BW, body weight; CAN, Canola oil; FC, food consumption; FCh, free cholesterol; FFA, free fatty acid; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Glu, glucose; Life-shortening; MR, mineralocorticoid receptor; OGTT, oral glucose tolerance test; RAAS, renin-angiotensin-aldosterone system; Rapeseed (canola) oil; SHR, spontaneously hypertensive rat; SHRSP; SHRSP, stroke-prone spontaneously hypertensive rat; SOY, soybean oil; Sex difference; TCh, total cholesterol; TG, triglyceride; Testosterone; WKY rat, Wistar Kyoto rat.