The impact of age and sex on body composition and glucose sensitivity in C57BL/6J mice

Abstract

A paucity of data exists regarding sex differences in age‐related obesity and insulin resistance, particularly in the preclinical murine model. The purpose of this study was to determine the effects of age and sex on insulin action and body composition in C57BL/6J mice. Aged (AG, 18 months old) male C57BL/6J mice, glucose tolerance was diminished compared to young (YG, 6 months old) male mice (Area Under Curve: 95,103 ± 6818 vs. 64,005 ± 2031, P = 0.002). However, there was no age‐related decline in glucose or insulin tolerance in females. Body composition analysis revealed that AG males had significantly greater body mass (42.2 ± 1.9 vs. 30.0 ± 0.4 g, P < 0.0001), fat mass (18.7 ± 2.0 vs. 3.3 ± 0.4 g, P < 0.0001), body fat (43.0 ± 3.0 vs. 11.0 ± 1.5%, P < 0.0001) than YG males. In AG females, body mass (32.8 ± 1.6 vs. 26.3 ± 0.9 g, P = 0.02) was higher, but fat mass (13.3 ± 2.0 vs. 9.5 ± 1.3 g, P = 0.24) and body fat (37.8 ± 4.8 vs. 35.5 ± 3.8%, P = 0.67) were similar when compared to YG females. AG males had significantly higher body mass (42.2 ± 1.9 vs. 32.8 ± 1.6 g, P = 0.001) and fat mass (18.7 ± 2.0 vs. 13.3 ± 2.0 g, P = 0.04) compared to AG females; however, body fat (43.0 ± 3.0 vs. 37.8 ± 4.8%, P = 0.28) was similar. Six weeks of treatment with MitoQ, a mitochondrial‐targeted antioxidant, did not reverse age‐related obesity in male mice. Surprisingly, obesity and insulin resistance appear to be reversed in the oldest of the old male mice (28 vs. 20 months). Our findings indicate that female mice, unlike males, are protected from age‐related obesity and insulin resistance.

Low-Intensity Running and High-Intensity Swimming Exercises Differentially Improve Energy Metabolism in Mice With Mild Spinal Muscular Atrophy

“…In this way, it is important to note that the current study has been conducted only on male mice, in accordance with the original work we recently published on the neuroprotective effects of physical exercise in type 3 SMA-like mice (Chali et al, 2016). Nevertheless, it is now well described that the gender can inflict both the metabolic status (Medrikova et al, 2012; Venezia et al, 2016; Reynolds et al, 2019) and the exercise-induced benefits (Veldink et al, 2003; McMullan et al, 2016; Zhou et al, 2018). Thus, it seems crucial to evaluate if female SMA mice with the same genetic background than the males used in the present study could identically adapt to the same exercise protocols.…”

The effect of succinic acid on the metabolic profile in high‐fat diet‐induced obesity and insulin resistance

“…Animals were housed at the Skidmore College animal facility on a 12:12 light:dark cycle and had access to food and water ad libitum. After initial acclimatization (1 week), the mice were randomized into either a high‐fat diet (HFD; 60% kcal from fat) or a low‐fat diet (LFD; 10% kcal from fat) group and consumed their respective diet for 4.5 months (Test Diets; Bloom et al., 2020; Reynolds et al., 2019; Shortreed et al., 2009; Trajcevski et al., 2013). Using a randomized controlled design, during the final 8 weeks of the diet intervention, the groups were subsequently randomized to receive either vehicle (VEH, drinking water) or succinic acid (SA; 0.75 mg/ml in drinking water; Ferro, Carbone, Marzouk, et al., 2017; Ferro, Carbone, Zhang, et al., 2017; Figure 1).…”

“…To test glucose tolerance, the mice completed an overnight fast prior to receiving an intraperitoneal injection of glucose (2.0 g/kg body weight; Reynolds et al., 2019). Subsequently, venous blood from the tails was obtained (~5 µl) at 15, 30, 45, 60, 90, and 120 min post‐injection and blood glucose was assessed using a hand‐held glucometer (Accu‐Check, Roche Diabetes Care, Inc; Reynolds et al., 2019). In addition to the glucose tolerance test, insulin tolerance testing was also performed to assess insulin action.…”

“…To test glucose tolerance, the mice completed an overnight fast prior to receiving an intraperitoneal injection F I G U R E 1 Experimental overview. Experimental groups included high-fat diet succinic acid-treated (HFD-SA), high-fat diet vehicle (HFD-VEH), low-fat diet succinic acid-treated (LFD-SA), and low-fat diet vehicle (LFD-VEH) of glucose (2.0 g/kg body weight; Reynolds et al, 2019). Subsequently, venous blood from the tails was obtained (~5 µl) at 15, 30, 45, 60, 90, and 120 min post-injection and blood glucose was assessed using a hand-held glucometer (Accu-Check, Roche Diabetes Care, Inc; Reynolds et al, 2019).…”

High‐fat diet induced obesity and age influence the telomere shelterin complex and telomerase gene expression in mouse adipose tissue

“…Though, we acknowledge that measurements of telomere length and protein expression would make our current study more comprehensive, we believe that the findings of our study are the first to demonstrate the effects of diet-induced obesity and aging on adipose tissue regulation of genes involved in telomere dynamics and thus provide novel insight as well as a detailed roadmap for future studies. One additional factor future studies might consider is the exploration of possible associations of altered telomere dynamics with glucose tolerance and insulin sensitivity, as three months HFD induces insulin resistance in C57BL/6J young mice (Liu et al, 2015) and we (Reynolds et al, 2019) and others (Oh et al, 2016) have documented that changes might begin at 16 months, but are more pronounced at 20 months of age.…”