Testing the potency of nutritional interventions to modulate eicosanoid metabolism in adipose tissues and brite adipogenesis
Final Report Abstract
The increasing prevalence of obesity and the lack of effective treatments makes the development of novel therapeutic options highly necessary. In this light, the energy expending properties of brown and brite (brown-in-white) adipocytes are a considered a promising target. Both types of adipocytes utilize the energy stored in storage lipids to generate heat, consequently, increase energy expenditure. Recruitment of brite adipocytes provides a potential double benefit as these cells arise through the conversion of white adipocytes, the main storage cell of excessive fat. Thus, brite adipocytes not only increase energy expenditure but also decrease fat mass. Conversion of white to brite adipocytes is naturally triggered by cold temperatures through signaling of endogenous norepinephrine. However, several other compounds are discussed to stimulate the recruitment of brite adipocytes in mice, in vitro as well as in vivo. Of those several belong to a group of ω6- and ω3-polyunsaturated fatty acid (PUFA) derivatives, termed oxylipins. The fatty acid origin renders this group of potent signaling molecules a favorable treatment option, as their abundance can be regulated by dietary supplementation of their respective PUFA precursor. Especially ω3-PUFA have been linked to beneficial health effects. However, evidence from studies demonstrating an energy balance regulating effect of oxylipins and dietary supplementation of ω6- and ω3-PUFA in a human context are scarce. Consequently, the transferability of murine study results is poorly researched. In this project we applied oxylipin profiling in murine and human brown, brite and white adipose tissue samples. We demonstrate that oxylipins are a marker for brown but not brite adipose tissue in both mice and humans, substantiating the similarity between murine brite and human brown adipose tissue. We identified two oxylipins (5-HETE and 5,6-EET), associated to the abundance of brown and brite adipocytes, that have not been previously described in this context. Additionally, we performed a nutritional intervention in mice fed diets with different ratios of ω6- and ω3-PUFA to investigate the potential of increased precursor abundance to recruit brite and brown adipocytes. To increase transferability of our results we investigated mice at 30 °C in order to simulate the thermal environment of humans. We demonstrate that the dietary ω6/ω3-PUFA ratio does not augment the recruitment of thermogenic capacity or influence body weight development, at a human-like thermal environment. This needs to be addressed by follow up research to increase translatability of results to humans and to save resources.
Publications
- (2018) Fatty Acid Metabolites as Novel Regulators of Non-shivering Thermogenesis. In: Pfeifer A., Klingenspor M., Herzig S. (eds) Brown Adipose Tissue. Handbook of Experimental Pharmacology, vol 251. Springer, Cham
Maurer SF, Dieckmann S, Kleigrewe K, Colson C, Amri EZ, Klingenspor M.
(See online at https://doi.org/10.1007/164_2018_150) - (2020) Fatty Acid Metabolite Profiling Reveals Oxylipins as Markers of Brown but Not Brite Adipose Tissue. Front Endocrinol 11:73
Dieckmann S, Maurer SF, Fromme T, Colson C, Virtanen KA, Amri EZ, Klingenspor M
(See online at https://doi.org/10.3389/fendo.2020.00073) - (2020) No Effect of Dietary Fish Oil Supplementation on the Recruitment of Brown and Brite Adipocytes in Mice or Humans under Thermoneutral Conditions. Mol Nutr Food Res 2000681
Maurer SF, Dieckmann S, Lund J, Fromme T, Hess AL, Colson C, Kjølbæk L, Astrup A, Gillum MP, Larsen LH, Liebisch G, Amri EZ, Klingenspor M
(See online at https://doi.org/10.1002/mnfr.202000681) - (2020) Uncoupling protein 1 and the capacity for nonshivering thermogenesis are components of the glucose homeostatic system. American Journal of Physiology-Endocrinology and Metabolism 318:2, E198-E215
Maurer SF, Fromme T, Mocek S, Zimmermann A, Klingenspor M
(See online at https://doi.org/10.1152/ajpendo.00121.2019) - (2020). The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes. Cells 9, no. 11: 2433
Colson C, Batrow PL, Gautier N, Rochet N, Ailhaud G, Peiretti F, Amri EZ
(See online at https://doi.org/10.3390/cells9112433)
