No Effect of Dietary Fish Oil Supplementation on the Recruitment of Brown and Brite Adipocytes in Mice or Humans under Thermoneutral Conditions

Abstract

Scope Brown and brite adipocytes within the mammalian adipose organ provide non‐shivering thermogenesis and thus, have an exceptional capacity to dissipate chemical energy as heat. Polyunsaturated fatty acids (PUFA) of the n3‐series, abundant in fish oil, have been repeatedly demonstrated to enhance the recruitment of thermogenic capacity in these cells, consequently affecting body adiposity and glucose tolerance. These effects are scrutinized in mice housed in a thermoneutral environment and in a human dietary intervention trial. Methods and results Mice are housed in a thermoneutral environment eliminating the superimposing effect of mild cold‐exposure on thermogenic adipocyte recruitment. Dietary fish oil supplementation in two different inbred mouse strains neither affects body mass trajectory nor enhances the recruitment of brown and brite adipocytes, both in the presence and absence of a β3‐adrenoreceptor agonist imitating the effect of cold‐exposure on adipocytes. In line with these findings, dietary fish oil supplementation of persons with overweight or obesity fails to recruit thermogenic adipocytes in subcutaneous adipose tissue. Conclusion Thus, the authors' data question the hypothesized potential of n3‐PUFA as modulators of adipocyte‐based thermogenesis and energy balance regulation.

PET/MRI-evaluated brown adipose tissue activity may be related to dietary MUFA and omega-6 fatty acids intake

“…It was noted that diets rich in ARA favor WAT formation by preventing the “browning” process 52 . However, recently published results suggest no effect of dietary fish oil supplementation on the recruitment of brown and brite adipocytes in mice or humans under thermoneutral conditions 53 . The thermoneutral conditions could be an explanation of noted conflicting results, since different circulating PUFA and oxylipins (being the lipid mediators produced from PUFA) profiles in BAT-positive and BAT-negative subjects were noted 54 and cold exposure significantly increased plasma lipid composition only in BAT-positive individuals, strongly supporting the relationship between BAT and PUFA.…”

Brown Adipose Tissue—A Translational Perspective

“…Another recent study showed a similar antiobesity effect and stimulation of energy expenditure with fish oil supplementation in wild-type or UCP1 KO mice ( 734 ), suggesting that activation of BAT thermogenesis was not responsible for the effects of this treatment. Fish oil supplements in humans increased WAT browning in one report ( 735 ) but not in another ( 733 ). An association was reported between BAT 18 FDG uptake with fasting plasma DHA and EPA in humans ( 736 ).…”

“…In contrast, treatment with ethyl EPA (icosapent ethyl) was shown to confer important cardiovascular benefits in high-risk participants in a large, randomized controlled trial ( 727 ). Despite some early reports of increased expression of iBAT UCP1 and thermogenic gene expression, increased BAT mass and induction of WAT browning with fish oil supplementation in rodents ( 728–732 ), a more recent report did not reproduce these findings under thermoneutral conditions ( 733 ). Another recent study showed a similar antiobesity effect and stimulation of energy expenditure with fish oil supplementation in wild-type or UCP1 KO mice ( 734 ), suggesting that activation of BAT thermogenesis was not responsible for the effects of this treatment.…”

Metformin and vitamin D modulate adipose-derived stem cell differentiation towards the beige phenotype

“…Human studies currently show that activation of thermogenic adipose tissue is associated with a small and negligible loss of fat mass [ 65 ] . Moreover, no dietary intervention has yet been shown to affect Ucp1 expression, which is only expressed at extremely low levels in subcutaneous fat depots [ 66 , 67 ] . Several authors demonstrated the effect of 5 mM metformin in the modulation of cell behaviour [ 68–70 ] , as well as of vitamin D, involved in osteogenic differentiation [ 34 , 71 ] .…”