Structure–effect relation of C18 long-chain fatty acids in the reduction of body weight in rats

Abstract

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)). Design: Ad libitum fed, lean Wistar Kyoto rats treated orally with up to 600 mg kg À1 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. Measurements: 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. Conclusion: 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 pathwaydependent transcription factor CREB, most probably as part of a transdifferentiation process accompanied by enhanced energy expenditure.

Interactions of fatty acids with phosphatidylethanolamine membranes: X-ray diffraction and molecular dynamics studies

“…Although these results do not fi rmly establish the molecular mechanism of action of 2OHOA, they indicate that the observed alteration of biophysical membrane parameters in vitro also occurs in vivo and should have pharmacological relevance. In addition, a similar observation regarding body weight homeostasis could be made because neither SA nor EA were able to reduce body weight in rats, while OA showed a slight and 2OHOA a strong lipolytic effect on adipose tissue mass ( 40 ).…”

Could burning fat start with a brite spark? Pharmacological and nutritional ways to promote thermogenesis

“…Despite this, whole‐body oxygen consumption levels are elevated following olive oil consumption . The olive oil component oleic acid has no effect on BAT or WAT UCP1 mRNA levels, but the synthetic derivative 2‐hydroxyoleic acid decreases body weight and fat levels and increases WAT (but not BAT) UCP1 mRNA levels .…”

A chromatin perspective of adipogenesis

“…The existence of a common adipose precursor cell for brown and white fat cells was supported by the ability of white adipocytes to transdifferentiate into BAT cells under certain conditions. [61][62][63][64] Several in vitro studies support the differentiation of white preadipocytes into brown adipocytes and aim to identify the factors implicated in this switch in cell fate. Thus, functional inactivation of the retinoblastoma protein (pRb) in mouse embryo fibroblasts (MEFs) and in white preadipocytes results in increased differentiation of adipose cells with a gene expression pattern consistent with that of brown adipocytes.…”