Showing papers by "Dennis B. Lubahn published in 2021"

Role of ERβ in adipocyte metabolic response to wheel running following ovariectomy

Abstract: Estrogen receptor  (ERb), one of the two major estrogen receptors, acts via genomic and non-genomic signaling pathways to affect many metabolic functions, including mitochondrial biogenesis and respiration. This study assessed the effect of ERb classical genomic activity on adipocyte-specific and systemic metabolic responses to wheel running exercise in a rodent model of menopause. Female mice lacking the ERb DNA-binding domain (ERbDBDKO, N = 20) and wild-type (WT, N = 21) littermate controls were fed high-fat diet (HFD), ovariectomized (OVX), and randomized to control (no running wheel) and exercise (running wheel access) groups and were followed for eight weeks. Wheel running did not confer protection against metabolic dysfunction associated with HFD+OVX in either ERbDBDKO or WT mice, despite increased energy expenditure. Unexpectedly, in the ERbDBDKO group, wheel running increased fasting insulin and surrogate measures of insulin resistance, and modestly increased adipose tissue inflammatory gene expression (P<0.05). These changes were not accompanied by significant changes in adipocyte mitochondrial respiration. It was demonstrated for the first time, that female WT OVX mice do experience exercise-induced browning of white adipose tissue, indicated by a robust increase in uncoupling protein 1 (UCP1) (P<0.05). However, KO mice were completely resistant to this effect, indicating that full ERb genomic activity is required for exercise-induced browning. The inability to upregulate UCP1 with exercise following OVX may have resulted in the increased insulin resistance observed in KO mice, a hypothesis requiring further investigation.

Voluntary Wheel Running Partially Compensates for the Effects of Global Estrogen Receptor-α Knockout on Cortical Bone in Young Male Mice.

Abstract: Estrogen receptor-α knockout (ERKO) in female, but not male, mice results in an impaired osteogenic response to exercise, but the mechanisms behind this ability in males are unknown. We explored the main and interactive effects of ERKO and exercise on cortical geometry, trabecular microarchitecture, biomechanical strength, and sclerostin expression in male mice. At 12 weeks of age, male C57BL/6J ERKO and WT animals were randomized into two groups: exercise treatment (EX) and sedentary (SED) controls, until 22 weeks of age. Cortical geometry and trabecular microarchitecture were measured via μCT; biomechanical strength was assessed via three-point bending; sclerostin expression was measured via immunohistochemistry. Two-way ANOVA was used to assess sclerostin expression and trabecular microarchitecture; two-way ANCOVA with body weight was used to assess cortical geometry and biomechanical strength. ERKO positively impacted trabecular microarchitecture, and exercise had little effect on these outcomes. ERKO significantly impaired cortical geometry, but exercise was able to partially reverse these negative alterations. EX increased cortical thickness regardless of genotype. There were no effects of genotype or exercise on sclerostin expression. In conclusion, male ERKO mice retain the ability to build bone in response to exercise, but altering sclerostin expression is not one of the mechanisms involved.