Identification of differences in human and great ape phytanic acid metabolism that could influence gene expression profiles and physiological functions

Abstract

BackgroundIt has been proposed that anatomical differences in human and great ape guts arose in response to species-specific diets and energy demands. To investigate functional genomic consequences of these differences, we compared their physiological levels of phytanic acid, a branched chain fatty acid that can be derived from the microbial degradation of chlorophyll in ruminant guts. Humans who accumulate large stores of phytanic acid commonly develop cerebellar ataxia, peripheral polyneuropathy, and retinitis pigmentosa in addition to other medical conditions. Furthermore, phytanic acid is an activator of the PPAR-alpha transcription factor that influences the expression of genes relevant to lipid metabolism.ResultsDespite their trace dietary phytanic acid intake, all great ape species had elevated red blood cell (RBC) phytanic acid levels relative to humans on diverse diets. Unlike humans, chimpanzees showed sexual dimorphism in RBC phytanic acid levels, which were higher in males relative to females. Cultured skin fibroblasts from all species had a robust capacity to degrade phytanic acid. We provide indirect evidence that great apes, in contrast to humans, derive significant amounts of phytanic acid from the hindgut fermentation of plant materials. This would represent a novel reduction of metabolic activity in humans relative to the great apes.ConclusionWe identified differences in the physiological levels of phytanic acid in humans and great apes and propose this is causally related to their gut anatomies and microbiomes. Phytanic acid levels could contribute to cross-species and sex-specific differences in human and great ape transcriptomes, especially those related to lipid metabolism. Based on the medical conditions caused by phytanic acid accumulation, we suggest that differences in phytanic acid metabolism could influence the functions of human and great ape nervous, cardiovascular, and skeletal systems.

Comparative RNA sequencing reveals substantial genetic variation in endangered primates

“…While there are known functional differences between macaque and rodent peroxisomes (Hoivik et al 2004), comparative data from dogs suggested that those differences are likely explained by derived changes in rodents, not primates (Foxworthy et al 1990). Differences have also been observed in peroxisomal gene functioning and peroxisomal lipid metabolism between apes or humans and other primates (Somel et al 2008;Keebaugh and Thomas 2010;Watkins et al 2010). In contrast, our results suggest a different, major biological distinction in the regulation of peroxisomerelated genes between all primates and other mammals, possibly driven by adaptive events that occurred in the ancestral primate lineage.…”

Пероксисомні Біогенні Порушення В Спектрі Синдрому Цельвегера: Діагностика, Моніторинг І Лікування Відповідно До Рекомендацій Глобальної Фундації Пероксисомних Захворювань

“…Она находится в жирах жвачных животных, молоч-ных продуктах и некоторых сортах рыбы [39]. Таким образом, повышение уровня фитановой кислоты в плазме можно устранить с помощью диетического ограничения [39].…”

Phytanic acid, a daily consumed chlorophyll-yielded phytol bio-metabolite: A comprehensive review

“…PA can be obtained as RBC bound stuff (Watkins et al, 2010), which could serve as a biomarker for evaluating digestive health (Moser et al, 2013) and influence the functions of nervous, cardiovascular, and skeletal systems in human and great apes (Watkins et al, 2010).…”

“…However, Gloerich et al (2007) demonstrated that peroxisome proliferator-activated receptor-alpha (PPARα) is responsible for PYT metabolism to PA in mice (Watkins et al, 2010). Ruminants and great captive apes/cohort of humans (e.g.…”