Brain changing tubers: Gene expression changes following mediaeval tuber consumption

Discovered in the remnants of waste at Soutra Aisle, Scotland's largest medieval hospital, the tubers of Lathyrus linifolius are thought to have hunger suppressing capabilities dating back to the 1700 s. Sir Robert Sibbald, founding member of the Royal College of Physicians, spoke about these tubers in his book “Provision for the Poor in time of Dearth and Scarcity” [1]. It is also thought that these tubers provided a boost of energy, and were used when soldiers were at war. The active component is suspected to be trans-anethole, although this has still to be confirmed. The aim of this study was to determine if the traditional usage of these tubers could help in the development of therapeutics for the future. Following initial in vitro cytotoxicity screening on various cell lines (HS27, PNT2, ZR75, U937, SHSY5Y, 3T3-L1, Hek293), and a preliminary feeding trial on Sprague Dawley rats (n = 2), it was found that both the solvent extracts and the full tuber (powdered) showed no toxicity at the concentrations tested (100 µg/ml-3.125 µg/ml in vitro; 42 mg/kg body weight, based on traditional dosage, in vivo). Subsequently, a larger in vivo feeding trial (n = 8 per group) was carried out to assess the appetite suppressing capabilities. This study showed no effect on body weight, food intake or water intake following treatment with the tuber in comparison to the control group (0.9% saline), and a second test group (treated with trans-anethole at 42 mg/kg BW). Appetite and hunger are complex processes controlled primarily in the hypothalamus [2]. To determine if the tuber has any effect on gene expression in the hypothalamus, the subjects were sacrificed and the hypothalamus dissected. RNA was extracted from the hypothalamus and RNA sequencing was carried out in a preliminary study (n = 1). The results evidently show that this tuber has an effect at RNA level, with 565 genes being upregulated (> 2-fold), and 642 genes being downregulated (> 2-fold) in comparison to the control group.

Acknowledgements: NW is funded by BBSRC. The authors are thankful to Dr Brian Moffat for his knowledge of Soutra Aisle and guidance on traditional usage, Mark Goff (Bitter-Vetch Ltd) who provided the tubers, and Dr. Greg Kenicer (Royal Botanic Gardens Edinburgh) who helped to identify the plant species and its' tubers.

Keywords: Appetite, Hunger, Mediaeval plant, RNA-Seq, Gene Expression.

References:

[1] Sibbald R. Provision for the Poor in time of Dearth and Scarcity. Early History of Food, 2^nd edition. Wing: Edinburgh; 1699

[2] Yeo G S H, Heisler L K. Unraveling the brain regulation of appetite: lessons from genetics. Nat Neurosci 2012; 15: 1343 – 1349