Higher Ambulatory Activity Research Articles

Metabolic Profiling of Mice with Deletion of the Orphan G Protein-Coupled Receptor, GPR37L1

Understanding the neurogenic causes of obesity may reveal novel drug targets to counter the obesity crisis and associated sequelae. Here, we investigate whether the deletion of GPR37L1, an astrocyte-specific orphan G protein-coupled receptor, affects whole-body energy homeostasis in mice. We subjected male Gpr37l1−/− mice and littermate wildtype (Gpr37l1+/+, C57BL/6J background) controls to either 12 weeks of high-fat diet (HFD) or chow feeding, or to 1 year of chow diet, with body composition quantified by EchoMRI, glucose handling by glucose tolerance test and metabolic rate by indirect calorimetry. Following an HFD, Gpr37l1−/− mice had similar glucose handling, body weight and fat mass compared with wildtype controls. Interestingly, we observed a significantly elevated respiratory exchange ratio in HFD- and chow-fed Gpr37l1−/− mice during daylight hours. After 1 year of chow feeding, we again saw no differences in glucose and insulin tolerance or body weight between genotypes, nor in energy expenditure or respiratory exchange ratio. However, there was significantly lower fat mass accumulation, and higher ambulatory activity in the Gpr37l1−/− mice during night hours. Overall, these results indicate that while GPR37L1 may play a minor role in whole-body metabolism, it is not a viable clinical target for the treatment of obesity.

Identifying subgroups of community-dwelling older adults and their prospective associations with long-term knee osteoarthritis outcomes.

To identify subgroups of community-dwelling older adults and to assess their longitudinal associations with long-term osteoarthritis (OA) outcomes. 1046 older adults aged 50-80years were studied. At baseline, body mass index (BMI), pedometer-measured ambulatory activity (AA), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) determined knee pain and information on comorbidities were obtained. Tibial cartilage volume and bone-marrow lesions (BMLs) were assessed using MRI at baseline and 10years and total knee replacements (TKR) by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Latent class analysis was used to determine participant subgroups, considering baseline BMI, AA, pain and comorbidities, and linear mixed-effects or log-binomial models were used to assess the associations. Three subgroups/classes were identified: subgroup 1 (43%): Normal/overweight participants with higher AA, lower pain and lower comorbidities; subgroup 2 (32%): Overweight participants with lower AA, mild pain and higher comorbidities; subgroup 3 (25%): Obese participants with lower AA, mild pain and higher comorbidities. Subgroup 3 had greater cartilage volume loss (β - 60.56mm3, 95% CI - 105.91, - 15.21) and a higher risk of TKR (RR 3.19, 95% CI 1.75, 5.81), compared to subgroup 1. Subgroup 2 was not associated with cartilage volume change (β 13.06mm3, 95% CI - 30.87, 57.00) or risk of TKR (RR 1.16, 95% CI 0.56, 2.36), compared to subgroup 1. Subgroup membership was not associated with worsening BMLs. Our findings suggest the existence of homogeneous subgroups of participants and support the utility of identifying patterns of characteristics/risk factors that may cluster together and using them to identify subgroups of people who may be at a higher risk of developing and/or progressing OA. Key Points • Complex interplay among characteristics/factors leads to conflicting evidence between ambulatory activity and knee osteoarthritis. • Distinct subgroups are identifiable based on ambulatory activity, body mass index, knee pain, and comorbidities. • Identifying subgroups can be used to determine those who are at risk of developing/progressing osteoarthritis.

Pannexin 1 and Pannexin 3 regulate body fat accumulation in mouse models of dietinduced obesity

Pannexins (Panx) are channel‐forming glycoproteins important in paracrine signaling and cellular development. Panx1 and Panx3 are expressed in adipocytes and adipose stromal cells. We discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet, while Panx3 KO mice have reduced total fat mass and weigh less than WT controls. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain but showed an increase in glucose and insulin levels compared to WT. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory activity, and reduced sleep duration relative to their WT littermates on a high‐fat diet. To uncover the cellular mechanism responsible for the increased fat content in the Panx1 KO, we isolated primary cultures of adipose‐derived stromal cells (ASCs) from WT and KO fat pads. In WT ASCs we observed that Panx1 protein levels increase upon induction into an adipogenic lineage. ASCs isolated from Panx1 KO mice proliferate less but demonstrate enhanced adipogenic differentiation with increased intracellular lipid accumulation, glycerol‐3‐phosphate dehydrogenase (GPDH) enzyme activity, and adipokine secretion, as compared to WT ASCs. This was consistent with the increased adipocyte size (hypertrophy) and decreased adipocyte numbers observed in subcutaneous fat of the Panx1 KO mice compared to WT. Panx3 is also expressed in adipose stromal cells and Panx3 protein levels significantly increase in differentiated adipocytes. However, the effect of the Panx3 KO seems to be the opposite of the Panx1 KO, with decreased weight under a high fat diet and lower fat mass (even under a normal chow diet). We propose that Panx1 and Panx3 may play opposing roles in adipose stromal cells during the early stages of adipogenic proliferation and differentiation, regulating fat accumulation in vivo.Support or Funding InformationFunded by the Canadian Institutes of Health Research (CIHR) grants to SP and LFThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pannexin 1 regulates adipose stromal cell differentiation and fat accumulation

Pannexin 1 (Panx1) is a channel-forming glycoprotein important in paracrine signaling and cellular development. In this study, we discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain and blood markers of obesity as compared to WT controls, except for an increase in glucose and insulin levels. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory activity, and reduced sleep duration relative to their WT littermates on a high-fat diet. To uncover the cellular mechanism responsible for the increased fat content in the KO, we isolated primary cultures of adipose-derived stromal cells (ASCs) from WT and KO fat pads. In WT ASCs we observed that Panx1 protein levels increase upon induction into an adipogenic lineage. ASCs isolated from Panx1 KO mice proliferate less but demonstrate enhanced adipogenic differentiation with increased intracellular lipid accumulation, glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, and adipokine secretion, as compared to WT ASCs. This was consistent with the increased adipocyte size and decreased adipocyte numbers observed in subcutaneous fat of the Panx1 KO mice compared to WT. We concluded that Panx1 plays a key role in adipose stromal cells during the early stages of adipogenic proliferation and differentiation, regulating fat accumulation in vivo.

Allozymic polymorphism and genetic differentiation among populations of Calomys musculinus and Calomys laucha (Rodentia: Muridae) from eastern Argentina

Summary The genetic variability and divergence among natural populations of Calomys musculinus and C. laucha from eastern Argentina were examined by protein electrophoresis of 24 loci. High levels of genetic variability were found in both species when compared to other rodents and mammals. Mean expected heterozygosity (He) ranged from 0.112 to 0.156, proportion of polymorphic loci (P 95% ) from 37.5% to 50% and mean number of alleles per locus (A) of 1.6-1.7 for C. musculinus . H e from 0.097 to 0.126, P 95% from 34.8 to 39.1 and A from 1.7 to 1.9 were the values for C. laucha . Populations of this last species revealed a higher degree of geographical differentiation (Θ = 0.017, P C. musculinus (Θ = 0.002, P > 0.05). These results are in agreement with the known social structure and habitat of both species. C. musculinus is an opportunistic species, with a loose social structure and a predominance of transient over resident animals, indicating a high ambulatory activity. C. laucha , on the contrary, inhabits almost exclusively cultivated fields, and evidence of social stratification has been reported for this species.