Structure-effect relation of C18 long-chain fatty acids in the reduction of body weight in rats.
OBJECTIVE
To investigate the relationship between chemical structure and physiological effect, the efficacy and the molecular mechanisms involved in the reduction of body weight by C18 fatty acids (stearic, elaidic, oleic, linoleic and 2-hydroxyoleic acids (2-OHOA)).


METHODS
Ad libitum fed, lean Wistar Kyoto rats treated orally with up to 600 mg kg(-1) of the fatty acids or vehicle every 12 h for 7 days. Besides, starved rats and rats pairfed to the 2-OHOA-treated group served as additional controls under restricted feeding conditions.


METHODS
Body weight, food intake, weight of various fat depots, plasma leptin, hypothalamic neuropeptides, uncoupling proteins (UCP) in white (WAT) and brown adipose tissue (BAT) and phosphorylation level of cyclic AMP (cAMP) response element-binding protein (CREB) in WAT.


RESULTS
Only treatment with oleic acid and 2-OHOA induced body weight loss (3.3 and 11.4%, respectively) through reduction of adipose fat mass. Food intake in these rats was lower, although hypothalamic neuropeptide and plasma leptin levels indicated a rise in orexigenic status. Rats pairfed to the 2-hydroxyoleic group only lost 6.3% body weight. UCP1 expression and phosphorylation of CREB was drastically increased in WAT, but not BAT of 2-OHOA-treated rats, whereas no UCP1 expression could be detected in WAT of rats treated with oleic acid.


CONCLUSIONS
Both cis-configured monounsaturated C18 fatty acids (oleic acid and 2-OHOA) reduce body weight, but the introduction of a hydroxyl group in position 2 drastically increases loss of adipose tissue mass. The novel molecular mechanism unique to 2-hydroxyoleic, but not oleic acid, implies induction of UCP1 expression in WAT by the cAMP/PKA pathway-dependent transcription factor CREB, most probably as part of a transdifferentiation process accompanied by enhanced energy expenditure.
Vögler
O
O
Laboratory of Molecular and Cellular Biomedicine, Institut Universitari d'Investigació en Ciències de Salut, Department of Biology, University of Balearic Islands, Palma de Mallorca, Spain. oliver.vogler@uib.es
López-Bellan
A
A
Alemany
R
R
Tofé
S
S
González
M
M
Quevedo
J
J
Pereg
V
V
Barceló
F
F
Escriba
P V
PV
D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000502:physiology*; D005227:Fatty Acids / Q000008:administration & dosage*; D005247:Feeding Behavior; D015151:Immunoblotting; D020738:Leptin / Q000378:metabolism; D019787:Linoleic Acid / Q000008:administration & dosage; D009479:Neuropeptides / Q000378:metabolism; D019301:Oleic Acid / Q000008:administration & dosage; D009829:Oleic Acids / Q000008:administration & dosage; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013229:Stearic Acids / Q000008:administration & dosage; D013329:Structure-Activity Relationship
C483229:2-hydroxyoleic acid; D005227:Fatty Acids; D020738:Leptin; D009479:Neuropeptides; D009829:Oleic Acids; D013229:Stearic Acids; D019301:Oleic Acid; C011459:elaidic acid; C031183:stearic acid; D019787:Linoleic Acid