Different Statistical Approaches to Characterization of Adipocyte Size in Offspring of Obese Rats: Effects of Maternal or Offspring Exercise Intervention

Abstract

Adipocyte size (AS) shows asymmetric distribution related to current metabolic state, e.g., adipogenesis or lipolysis. We profiled AS distribution using different statistical approaches in offspring (F1) of control (C) and obese (MO) mothers (F0) with and without F0 or F1 exercise. Offspring from F0 exercise were designated CF0ex and MOF0ex. Exercised F1 of sedentary mothers were designated CF1ex and MOF1ex. F1 retroperitoneal fat cross-sectional AS was measured by median, cumulative distributions, data dispersion and extreme values based on gamma distribution modeling. F1 metabolic parameters: body weight, retroperitoneal fat, adiposity index (AI), serum leptin, triglycerides (TG) and insulin resistance index (IRI) were measured. Male and female F1 AS showed different cumulative distribution between C and MO (p < 0.0001) therefore comparisons were performed among C, CF0ex and CF1ex groups and MO, MOF0ex and MOF1ex groups. MO AI was higher than C (p < 0.05) and male MOF1ex AI lower than MO (p < 0.05). Median AS was higher in male and female MO vs. C (p < 0.05). Male and female MOF0ex and MOF1ex reduced median AS (p < 0.05). Lower AS dispersion was observed in male CF1ex and MOF1ex vs. CF0ex and MOF0ex, respectively. MO reduced small and increased large adipocyte proportions vs. C (p < 0.05); MOF0ex increased small and MOF1ex the proportion of large adipocytes vs. MO (p < 0.05). MOF0ex reduced male IRI and female TG vs. MO (p < 0.05). MOF1ex reduced male and female leptin (p < 0.05); CF1ex reduced male leptin (p < 0.05). Conclusions: several factors, diet, physical activity and gender modify AS distribution. Conventional AS distribution methods normally do not include analyzes of extreme, large and small adipocytes, which characterize different phenotypes. Maternal high fat diet affects F1 AS distribution, which was programmed during development. F0ex and F1ex have gender specific F1 beneficial effects. AS distribution characterization helps explain adipose tissue metabolic changes in different physiological conditions and will aid design of efficacious interventions to prevent and/or recuperate adverse developmental programming outcomes. Finally, precise identification of effects of specific interventions as exercise of F0 and/or F1 are needed to improve outcomes in obese women and their obesity prone offspring.

A distribution-centered approach for analyzing human adipocyte size estimates and their association with obesity-related traits and mitochondrial function

“…Our data indicate that histology-derived adipocyte cross-sectional area is characterized by positive skewness. Similar distribution shapes have been previously reported in rodents and humans [ 8 , 39 , 40 ]. We show that calculation of adipocyte diameter, volume or surface area from cross-sectional area introduces substantial changes to distribution shape.…”

The Effects of High-Protein Diet and Resistance Training on Glucose Control and Inflammatory Profile of Visceral Adipose Tissue in Rats

“…Studies examining the frequency distribution of adipose cells showed that adipocytes are not homogeneous in their ability to uptake lipids or their functional properties in response to a high-fat diet [45]. Ibáñez et al [46] explained that asymmetry in cell distribution is a critical outcome of proliferation and differentiation since small adipocytes are linked to an increased rate of adipocyte proliferation, and large adipocytes are associated with increased lipid storage capacity. The novel findings from this study are that HPD-Control displayed a nearly bimodal distribution of adipose cells, which suggests that high-protein diets associated with sedentarism can increase both mature and immature cells or cells incapable of maximally depositing triglyceride.…”

Developmental programming of insulin resistance: are androgens the culprits?

“…In stark contrast, a lack of change in the phosphorylation states of AKT, mTOR, ERK, GSK3B, and S6K during fetal life as well as increased mRNA expression of IR2, mTOR, AKT, PI3K, and peroxisome proliferator-activated receptor gamma (PPARγ) in the VAT with increased insulinstimulated phosphorylated-AKT in the VAT and SAT in adult female offspring of gestationally testosterone-treated sheep (Nada et al 2010) reflect an insulinsensitive state in adipose tissue. Whether these differences in adipose insulin sensitivity programmed by gestational insults is due to differences in the adipose depot examined, species-or sex-specific differences, developmental time point studied, or differences in adipocyte differentiation (adipocyte hypertrophy in PCOS and offspring of obese mice (Manneras-Holm et al 2011, Caldwell et al 2014, Ibanez et al 2018) vs adipocyte hypotrophy in gestational testosterone-treated sheep (Cardoso et al 2016)) requires further examination.…”