TY - JOUR
T1 - Selective cannabinoid-1 receptor blockade benefits fatty acid and triglyceride metabolism significantly in weight-stable nonhuman primates
AU - Vaidyanathan, Vidya
AU - Bastarrachea, Raul A.
AU - Higgins, Paul B.
AU - Saroja Voruganti, V.
AU - Kamath, Subhash
AU - Dipatrizio, Nicholas V.
AU - Piomelli, Daniele
AU - Comuzzie, Anthony G.
AU - Parks, Elizabeth J.
PY - 2012/9/1
Y1 - 2012/9/1
N2 - The goal of this study was to determine whether administration of the CB1 cannabinoid receptor antagonist rimonabant would alter fatty acid flux in nonhuman primates. Five adult baboons (Papio Sp) aged 12.1 ± 4.7 yr (body weight: 31.9 ± 2.1 kg) underwent repeated metabolic tests to determine fatty acid and TG flux before and after 7 wk of treatment with rimonabant (15 mg/day). Animals were fed ad libitum diets, and stable isotopes were administered via diet (d 31-tripalmitin) and intravenously ( 13C 4-palmitate, 13C 1-acetate). Plasma was collected in the fed and fasted states, and blood lipids were analyzed by GC-MS. DEXA was used to assess body composition and a hyperinsulinemic euglycemic clamp used to assess insulin-mediated glucose disposal. During the study, no changes were observed in food intake, body weight, plasma, and tissue endocannabinoid concentrations or the quantity of liver-TG fatty acids originating from de novo lipogenesis (19 ± 6 vs. 16 ± 5%, for pre- and posttreatment, respectively, P = 0.39). However, waist circumference was significantly reduced 4% in the treated animals (P < 0.04), glucose disposal increased 30% (P = 0.03), and FFA turnover increased 37% (P = 0.02). The faster FFA flux was consistent with a 43% reduction in these fatty acids used for TRL-TG synthesis (40 ± 3 vs. 23 ± 4%, P = 0.02) and a twofold increase in TRL-TG turnover (1.5 ± 0.9 vs. 3.1 ± 1.4 μmol·kg -1·h -1, P = 0.03). These data support the potential for a strong effect of CB1 receptor antagonism at the level of adipose tissue, resulting in improvements in fasting turnover of fatty acids at the whole body level, central adipose storage, and significant improvements in glucose homeostasis.
AB - The goal of this study was to determine whether administration of the CB1 cannabinoid receptor antagonist rimonabant would alter fatty acid flux in nonhuman primates. Five adult baboons (Papio Sp) aged 12.1 ± 4.7 yr (body weight: 31.9 ± 2.1 kg) underwent repeated metabolic tests to determine fatty acid and TG flux before and after 7 wk of treatment with rimonabant (15 mg/day). Animals were fed ad libitum diets, and stable isotopes were administered via diet (d 31-tripalmitin) and intravenously ( 13C 4-palmitate, 13C 1-acetate). Plasma was collected in the fed and fasted states, and blood lipids were analyzed by GC-MS. DEXA was used to assess body composition and a hyperinsulinemic euglycemic clamp used to assess insulin-mediated glucose disposal. During the study, no changes were observed in food intake, body weight, plasma, and tissue endocannabinoid concentrations or the quantity of liver-TG fatty acids originating from de novo lipogenesis (19 ± 6 vs. 16 ± 5%, for pre- and posttreatment, respectively, P = 0.39). However, waist circumference was significantly reduced 4% in the treated animals (P < 0.04), glucose disposal increased 30% (P = 0.03), and FFA turnover increased 37% (P = 0.02). The faster FFA flux was consistent with a 43% reduction in these fatty acids used for TRL-TG synthesis (40 ± 3 vs. 23 ± 4%, P = 0.02) and a twofold increase in TRL-TG turnover (1.5 ± 0.9 vs. 3.1 ± 1.4 μmol·kg -1·h -1, P = 0.03). These data support the potential for a strong effect of CB1 receptor antagonism at the level of adipose tissue, resulting in improvements in fasting turnover of fatty acids at the whole body level, central adipose storage, and significant improvements in glucose homeostasis.
KW - Adipose
KW - Baboon
KW - Endocannabinoid
KW - Fatty acid flux
KW - Stable isotopes
UR - http://www.scopus.com/inward/record.url?scp=84865769737&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00072.2012
DO - 10.1152/ajpendo.00072.2012
M3 - Article
C2 - 22761159
AN - SCOPUS:84865769737
SN - 0193-1849
VL - 303
SP - E624-E634
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 5
ER -