Effect of conjugated estrogens and bazedoxifene on glucose, energy and lipid metabolism in obese postmenopausal women

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.

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The Route of Estrogen Replacement Therapy Confers Divergent Effects on Substrate Oxidation and Body Composition in Postmenopausal Women

The Endocrinologist ◽

10.1097/00019616-199903000-00015 ◽

1999 ◽

Vol 9 (2) ◽

pp. 149

Author(s):

&NA;

Keyword(s):

Body Composition ◽

Replacement Therapy ◽

Postmenopausal Women ◽

Estrogen Replacement Therapy ◽

Substrate Oxidation ◽

Estrogen Replacement

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Meat quality traits and muscle composition of cows differing in lactation performance

Archives Animal Breeding ◽

10.5194/aab-55-36-2012 ◽

2012 ◽

Vol 55 (1) ◽

pp. 36-47 ◽

Cited By ~ 3

Author(s):

M. Hamada ◽

E. Albrecht ◽

A.-R. El Bagory ◽

A.-B. Edris ◽

H. M. Hammon ◽

...

Keyword(s):

Body Composition ◽

Cell Size ◽

Muscle Fibre ◽

Meat Quality ◽

Quality Traits ◽

Lactation Performance ◽

Fat Cell ◽

Muscle Structure ◽

Meat Quality Traits ◽

The Impact

Abstract. Beef and dairy cows differ in the way in which they utilise nutrients and in accretion or mobilisation of body reserves during lactation. Thus far, little is known about the impact of lactation performance on body composition, meat quality, and the related muscle structure of cows with a defined, combined beef and dairy genetic background. In the described experiment, 50 F2 cows, originating from mating Charolais bulls to German Holstein cows and a following intercross of F1 individuals, were slaughtered during the second lactation, 30 days after calving. Cows were assigned to 3 groups, each containing representatives of 3 families, according to lactation performance. Standard carcass and meat quality traits were determined. Additionally, samples from longissimus muscle were investigated by histology and computer image analysis for muscle fibre profile, intramuscular fat cell size, and marbling traits. Subcutaneous fat cell size was measured to estimate the impact of lactation on body fat reserves. The results suggest no influence of the duration of the first lactation on body composition, meat quality or muscle structure. However, the amount of milk per day influenced body weight, body composition, and marbling traits. Relationships between traits were low, but showed consistently that increasing milk yield was negatively correlated with tissue accretion. Changes of muscle fibre and fat cell profile, indicating protein or fat mobilisation by lactation, could not be detected. In the presented study, lactation had only minor consequences for meat quality.

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Aerobic Exercise And Insulin Sensitivity In Postmenopausal Women: Is Body Composition Implicated?

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000386113.02895.d7 ◽

2010 ◽

Vol 42 ◽

pp. 727-728

Author(s):

Eric Cormier ◽

Mathieu Maltais ◽

Isabelle Dionne

Keyword(s):

Body Composition ◽

Insulin Sensitivity ◽

Aerobic Exercise ◽

Postmenopausal Women

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Fat Cell Size: Measurement Methods, Pathophysiological Origins, and Relationships with Metabolic Dysregulations

Endocrine Reviews ◽

10.1210/endrev/bnab018 ◽

2021 ◽

Author(s):

Run Zhou Ye ◽

Gabriel Richard ◽

Nicolas Gévry ◽

André Tchernof ◽

André C Carpentier

Keyword(s):

Cell Size ◽

Measurement Methods ◽

Published Data ◽

Ectopic Fat ◽

Cardiovascular Disorders ◽

Fat Cell ◽

Fat Accumulation ◽

Metabolic Dysregulation ◽

Fat Cell Size ◽

Adipocyte Hypertrophy

Abstract The obesity pandemic increasingly causes morbidity and mortality from type 2 diabetes, cardiovascular diseases and many other chronic diseases. Fat cell size (FCS) predicts numerous obesity-related complications such as lipid dysmetabolism, ectopic fat accumulation, insulin resistance, and cardiovascular disorders. Nevertheless, the scarcity of systematic literature reviews on this subject is compounded by the use of different methods by which FCS measurements are determined and reported. In this paper, we provide a systematic review of the current literature on the relationship between adipocyte hypertrophy and obesity-related glucose and lipid dysmetabolism, ectopic fat accumulation, and cardiovascular disorders. We also review the numerous mechanistic origins of adipocyte hypertrophy and its relationship with metabolic dysregulation, including changes in adipogenesis, cell senescence, collagen deposition, systemic inflammation, adipokine secretion, and energy balance. To quantify the effect of different FCS measurement methods, we performed statistical analyses across published data while controlling for body mass index, age, and sex.

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Conjugated Estrogens and Bazedoxifene Improve β Cell Function in Obese Menopausal Women

Journal of the Endocrine Society ◽

10.1210/js.2019-00074 ◽

2019 ◽

Vol 3 (8) ◽

pp. 1583-1594 ◽

Cited By ~ 1

Author(s):

Dragana Lovre ◽

Erin Peacock ◽

Bonnie Katalenich ◽

Cynthia Moreau ◽

Beibei Xu ◽

...

Keyword(s):

Body Composition ◽

Postmenopausal Women ◽

Glucose Homeostasis ◽

Cell Function ◽

Model Assessment ◽

Β Cell ◽

Conjugated Estrogens ◽

Markers Of Inflammation ◽

Menopausal Women ◽

Β Cell Function

Abstract Context Studies suggest that menopausal hormone therapy (MHT) prevents type 2 diabetes (T2D). The combination of conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is an MHT that improves obesity and T2D in preclinical models of menopausal metabolic syndrome. The effect of CE/BZA on adiposity and glucose homeostasis in obese postmenopausal women is unknown. Objective To investigate the effect of CE/BZA on body composition, glucose homeostasis, and markers of inflammation in obese postmenopausal women. Research Design, Intervention, and Participants Randomized, double-blind, placebo-controlled pilot trial of 12 obese menopausal women assigned to 12-week treatment with CE 0.45 mg/BZA 20 mg (n = 7) or placebo (n = 5). At baseline and after 12 weeks, we assessed body composition (dual-energy X-ray absorptiometry), glucose homeostasis (IV glucose tolerance test), and inflammation biomarkers. Results Women treated with CE/BZA exhibited increased β cell function using homeostatic model assessment-B [median (interquartile range) CE/BZA vs placebo: 18.5 (−0.9 to 320.6) μU/mM vs −25.5 (−39.9 to −0.1) μU/mM; P = 0.045], and decreased basal glucose concentrations (Gb) [−5.2 (−9.2 to −1.7) mg/dL vs 2.7 (0.9 to 4.9) mg/dL; P = 0.029]. Insulin sensitivity was higher in the placebo arm [1.35 (1.12 to 1.82) (μU/mL) min−1 vs −0.24 (−1.50 to 0.19) (μU/mL) min−1; P = 0.029]. No changes between treatment groups were observed for the acute insulin response to glucose (AIRg), the disposition index (DI), body composition, and inflammatory biomarkers. Conclusions A 12-week treatment of obese postmenopausal women with CEs/BZA improves fasting β cell function and glucose concentrations without change in AIRg, HOMA-IR, DI, body composition, or markers of inflammation.

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