Femoral Bone Marrow Insulin Sensitivity Is Increased by Resistance Training in Elderly Female Offspring of Overweight and Obese Mothers

Abstract

Bone marrow insulin sensitivity may be an important factor for bone health in addition to bone mineral density especially in insulin resistant conditions. First we aimed to study if prenatal maternal obesity plays a role in determining bone marrow insulin sensitivity in elderly female offspring. Secondly we studied if a four-month individualized resistance training intervention increases bone marrow insulin sensitivity in elderly female offspring and whether this possible positive outcome is regulated by the offspring’s mother’s obesity status. 37 frail elderly females (mean age 71.9 ± 3.1 years) of which 20 were offspring of lean/normal-weight mothers (OLM, maternal BMI ≤ 26.3 kg/m2) and 17 were offspring of obese/overweight mothers (OOM, maternal BMI ≥ 28.1 kg/m2) were studied before and after a four-month individualized resistance training intervention. Nine age- and sex-matched non-frail controls (maternal BMI ≤ 26.3 kg/m2) were studied at baseline. Femoral bone marrow (FBM) and vertebral bone marrow (VBM) insulin sensitivity were measured using [18F]fluoro-2-deoxy-D-glucose positron emission tomography with computer tomography under hyperinsulinemic euglycemic clamp. We found that bone marrow insulin sensitivity was not related to maternal obesity status but FBM insulin sensitivity correlated with whole body insulin sensitivity (R = 0.487, p = 0.001). A four-month resistance training intervention increased FBM insulin sensitivity by 47% (p = 0.006) only in OOM, while VBM insulin sensitivity remained unchanged regardless of the maternal obesity status. In conclusion, FBM and VBM glucose metabolism reacts differently to a four-month resistance training intervention in elderly women according to their maternal obesity status.Trial RegistrationClinicalTrials.gov NCT01931540

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in systemic glucose homeostasis

“…Superficially, this seems at odds with two studies reporting that BM 18 F-FDG uptake correlates inversely with BM fat content (Huovinen et al, 2014; Schraml et al, 2015); however, on further consideration, it is clear that these findings are not inconsistent with ours. Indeed, we show that axial bones have less BMAT but greater BM 18 F-FDG uptake than humeri or femurs, mirroring these and other previous reports of 18 F-FDG uptake in whole BM (Huovinen et al, 2016). Importantly, unlike our approach, no previous studies have distinguished 18 F-FDG uptake between RM and BMAT specifically.…”

“…Thus, a unique advance of our work is the finding that, in axial bones, BMAT glucose uptake is greater than in bone and similar or greater than in RM. This is particularly notable given that both BM and bone are sites of high glucose uptake, capable of exceeding levels observed in WAT or skeletal muscle (Huovinen et al, 2016; Huovinen et al, 2014; Zoch et al, 2016) (Fig. 4, Fig.…”

“…Unlike WAT and BAT, the role of BMAT in systemic energy metabolism is poorly understood. Previous studies have shed some light on BMAT lipid metabolism in vivo (Scheller et al, 2018; Tran et al, 1981), and PET/CT has been used to assess glucose uptake into bones or BM (Huovinen et al, 2016; Huovinen et al, 2014; Nishio et al, 2012; Zoch et al, 2016); however, our study is the first to characterise in vivo glucose metabolism specifically in BMAT. Our data provide key insights into how BMAT compares to WAT and BAT; reveal new site-specific differences in BMAT characteristics; and identify BMAT as a major site of skeletal glucose disposal.…”

“…For example, adipocyte-specific ablation of Insr in mice decreases BMAd size (Qiang et al, 2016), suggesting a role for insulin in BMAd lipogenesis; however, it is unclear if this is through de novo lipogenesis from glucose, or via insulin regulating uptake and esterification of fatty acids. In humans, Huovinen et al used PET/CT to assess BM 18 F-FDG uptake during hyperinsulinaemic euglycemic clamp, concluding that whole BM may be insulin-responsive (Huovinen et al, 2016). Thus, one possibility is that insulin can stimulate BMAT glucose uptake under hyperinsulinaemic conditions.…”

“…Despite these advances in understanding of BMAT lipid metabolism, its insulin responsiveness and role in systemic glucose homeostasis is poorly understood. PET/CT studies have demonstrated glucose uptake into whole bones or BM of animal models and humans (Huovinen et al, 2016; Huovinen et al, 2014; Nishio et al, 2012; Zoch et al, 2016), but uptake specifically into BMAT has not previously been examined. Whether BMAT is BAT- or beige-like is also debated (Scheller et al, 2016).…”