Kara L Marlatt1, Dragana Lovre2,3, Robbie A Beyl1, Chandra R Tate2, Evelyn K Hayes4, Charles F Burant5, Eric Ravussin1, Franck Mauvais-Jarvis2,3. 1. Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA. 2. Tulane University Health Sciences Center, New Orleans, Louisiana, USA. 3. Southeast Louisiana Veterans Administration Healthcare System, New Orleans, Louisiana, USA. 4. Baton Rouge General Hospital, Baton Rouge, Louisiana, USA. 5. Departments of Internal Medicine, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Abstract
OBJECTIVE: Combining conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is a novel, orally administered menopausal therapy. We investigated the effect of CE/BZA on insulin sensitivity, energy metabolism, and serum metabolome in postmenopausal women with obesity. DESIGN: Randomized, double-blind, crossover pilot trial with washout was conducted at Pennington Biomedical Research Center. Eight postmenopausal women (age 50-60 years, BMI 30-40 kg/m2) were randomized to 8 weeks CE/BZA or placebo. Primary outcome was insulin sensitivity (hyperinsulinemic-euglycemic clamp). Secondary outcomes included body composition (DXA); resting metabolic rate (RMR); substrate oxidation (indirect calorimetry); ectopic lipids (1H-MRS); fat cell size, adipose and skeletal muscle gene expression (biopsies); serum inflammatory markers; and serum metabolome (LC/MS). RESULTS: CE/BZA treatment produced no detectable effect on insulin sensitivity, body composition, ectopic fat, fat cell size, or substrate oxidation, but resulted in a non-significant increase in RMR (basal: P = 0.06; high-dose clamp: P = 0.08) compared to placebo. CE/BZA increased serum high-density lipoprotein (HDL)-cholesterol. CE/BZA also increased serum diacylglycerol (DAG) and triacylglycerol (TAG) species containing long-chain saturated, mono- and polyunsaturated fatty acids (FAs) and decreased long-chain acylcarnitines, possibly reflecting increased hepatic de novo FA synthesis and esterification into TAGs for export into very low-density lipoproteins, as well as decreased FA oxidation, respectively (P < 0.05). CE/BZA increased serum phosphatidylcholines, phosphatidylethanolamines, ceramides, and sphingomyelins, possibly reflecting the increase in serum lipoproteins (P < 0.05). CONCLUSIONS: A short treatment of obese postmenopausal women with CE/BZA does not alter insulin action or ectopic fat but increases serum markers of hepatic de novo lipogenesis and TAG production.
OBJECTIVE: Combining conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is a novel, orally administered menopausal therapy. We investigated the effect of CE/BZA on insulin sensitivity, energy metabolism, and serum metabolome in postmenopausal women with obesity. DESIGN: Randomized, double-blind, crossover pilot trial with washout was conducted at Pennington Biomedical Research Center. Eight postmenopausal women (age 50-60 years, BMI 30-40 kg/m2) were randomized to 8 weeks CE/BZA or placebo. Primary outcome was insulin sensitivity (hyperinsulinemic-euglycemic clamp). Secondary outcomes included body composition (DXA); resting metabolic rate (RMR); substrate oxidation (indirect calorimetry); ectopic lipids (1H-MRS); fat cell size, adipose and skeletal muscle gene expression (biopsies); serum inflammatory markers; and serum metabolome (LC/MS). RESULTS: CE/BZA treatment produced no detectable effect on insulin sensitivity, body composition, ectopic fat, fat cell size, or substrate oxidation, but resulted in a non-significant increase in RMR (basal: P = 0.06; high-dose clamp: P = 0.08) compared to placebo. CE/BZA increased serum high-density lipoprotein (HDL)-cholesterol. CE/BZA also increased serum diacylglycerol (DAG) and triacylglycerol (TAG) species containing long-chain saturated, mono- and polyunsaturated fatty acids (FAs) and decreased long-chain acylcarnitines, possibly reflecting increased hepatic de novo FA synthesis and esterification into TAGs for export into very low-density lipoproteins, as well as decreased FA oxidation, respectively (P < 0.05). CE/BZA increased serum phosphatidylcholines, phosphatidylethanolamines, ceramides, and sphingomyelins, possibly reflecting the increase in serum lipoproteins (P < 0.05). CONCLUSIONS: A short treatment of obese postmenopausal women with CE/BZA does not alter insulin action or ectopic fat but increases serum markers of hepatic de novo lipogenesis and TAG production.
Authors: Yogendra Kharode; Peter V N Bodine; Christopher P Miller; C Richard Lyttle; Barry S Komm Journal: Endocrinology Date: 2008-08-14 Impact factor: 4.736
Authors: JoAnn V Pinkerton; Jennifer A Harvey; Kaijie Pan; John R Thompson; Kelly A Ryan; Arkadi A Chines; Sebastian Mirkin Journal: Obstet Gynecol Date: 2013-05 Impact factor: 7.661
Authors: E Ravussin; C Bogardus; R S Schwartz; D C Robbins; R R Wolfe; E S Horton; E Danforth; E A Sims Journal: J Clin Invest Date: 1983-09 Impact factor: 14.808
Authors: Magdalena Pasarica; Hui Xie; David Hymel; George Bray; Frank Greenway; Eric Ravussin; Steven R Smith Journal: Diabetes Care Date: 2009-02-19 Impact factor: 17.152
Authors: Kara L Marlatt; Dragana Lovre; Robbie A Beyl; Chandra R Tate; Evelyn K Hayes; Charles F Burant; Eric Ravussin; Franck Mauvais-Jarvis Journal: Eur J Endocrinol Date: 2020-10 Impact factor: 6.664
Authors: Kara L Marlatt; Dori R Pitynski-Miller; Kathleen M Gavin; Kerrie L Moreau; Edward L Melanson; Nanette Santoro; Wendy M Kohrt Journal: Obesity (Silver Spring) Date: 2022-01 Impact factor: 5.002