Effects of Combined Oleoyl-Estrone and Rimonabant on Overweight Rats

Abstract

Abstract. Oleoyl-estrone (OE) decreases appetite, maintains energy expediture, induces lipolysis (sparing protein), and decreases cholesterolemia and insulin resistance. Rimonabant (SR141716) is a cannabinoid-receptor inhibitor that decreases appetite and mobilizes fat. We studied whether their combination improves their slimming effects. Male overweight rats received daily gavages of 5.3 mg / kg OE, 10 mg/ kg rimonabant, or both drugs during 10 days. Body weight and composition, energy balance, adipose tissue weight, and serum hormones and metabolites were measured. OE halved food intake and maintained energy expenditure at the expense of body fat. Rimonabant effects on appetite and energy balance were less marked, resulting in lower lipid mobilization. OE and rimonabant followed the OE pattern, with no additive or synergic effects. Glycemia was maintained, but OE decreased insulin, GLP-1, and cholesterol, whilst rimonabant increased cholecystokinin and cholesterol, and decreased NEFA. Both drugs decreased leptin and triacylglycerols; ghrelin was unchanged. The results hint at different mechanisms of action of both drugs: we can assume that OE effects do not involve the cannabinoid pathway. OE does not seem to act, either, after 10 days, through the secretion of ghrelin or the intestinal appetite-controlling peptides tested.

Rimonabant prevents additional accumulation of visceral and subcutaneous fat during high-fat feeding in dogs

“…4B). This transience in the effect of rimonabant on food intake has been consistently reported in rodent studies (9,11,35,36). Importantly, we did not find a correlation between food intake and body weight changes.…”

“…Obese mice treated with rimonabant decreased epididymal, perirenal, and lumbar fat depots (36) after 40 days of treatment. Similarly, rats treated with rimonabant for 10 -14 days showed a decrease in total body fat (9) and subcutaneous, retroperitoneal, mesenteric, and epididymal fat (11). A recent report has demonstrated a significant reduction in visceral fat in mice treated with rimonabant for 6 wk concomitant with a candy diet (16).…”

“…One of the compounds that can affect obesity is rimonabant, a selective type 1 cannabinoid receptor (CB1R) antagonist (7,34,39). Rimonabant has been reported to decrease appetite and body weight, although the former effect seems to be transient and might not explain the sustained body weight loss (9,11,35,36).…”

Cafeteria diet induce changes in blood flow that are more related with heat dissipation than energy accretion

“…Two groups of 12 animals were randomly selected and were fed ad libitum for 30 days with either normal rat chow (#2014 Harlan) or a simplified hyperlipidic cafeteria diet (Esteve et al, 1992b); the groups were named “control” and “cafeteria,” respectively. The rats were housed in 2-rat cages, and were kept in a controlled environment (lights on from 08:00 to 20:00; 21.5–22.5 °C; 50–60% humidity).…”

“…They had free access to water. The rats in the Cafeteria group were fed with fresh offerings of excess chow pellet, liver pâté spread on cookies, bacon and milk enriched with 300 g/L sucrose and 10 g/L of a protein, vitamin and mineral supplement (Meritene, Nestlé Nutrition, Barcelona, Spain) (Esteve et al, 1992a; Esteve et al, 1992b). Consumption of every item in the CD was recorded daily and converted into nutrient/energy equivalents to establish the actual intake of nutrients in their food selected by the cafeteria group.…”