Long-Term Improvement in Cardiorespiratory Fitness Ameliorates Insulin Sensitivity beyond Changes in Visceral/Ectopic Fat among Men with Visceral Obesity.

The SYNERGIE study documented the effects on cardiometabolic risk (CMR) indices of a 1-year lifestyle intervention targeting physical activity (PA) and diet followed by a 2-year maintenance period in men with visceral obesity. Improvements in CMR markers and a decrease in low-attenuation muscle (LAM) area were observed after 1 year. Despite a rebound in visceral adipose tissue (VAT) during the maintenance period, insulin resistance (IR) improved. We tested the hypothesis that variations in cardiorespiratory fitness (CRF) and LAM could explain the long-term improvement in IR. A health (n = 88; mean age 49.0 ± 8.2 years) and fitness (n = 72) evaluation was performed at 0, 1, and 3 years. Participants were classified into two groups based on their CRF response over the maintenance period (worsening: CRF- vs. maintenance/improvement: CRF+). During the maintenance period, changes in the psoas and core LAM areas correlated with changes in IR (r = 0.27; p < 0.05 and r = 0.34; p < 0.005) and changes in CRF (r = -0.31; p < 0.01 and r = -0.30; p < 0.05). IR improved in the CRF+ group (p < 0.05) but remained stable in the CRF- group. Men in the CRF+ group regained half of the changes in VAT volume and LAM at the psoas and mid-thigh compared to the CRF- group (p < 0.05). These results support the importance of targeting VAT and CRF/PA for the long-term management of CMR in men with visceral obesity.

Plasma IGFBP-2 levels reveal heterogeneity in hepatic fat content in adults with excess visceral adiposity.

Lay summary: Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms. Aim/hypothesis: Although excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes. Methods: A sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL). Results: Individuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001). Conclusion: In the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity.

Associations of insulin-like growth factor binding protein-2 with metabolic profile and hepatic fat deposition in asymptomatic men and women.

Low circulating levels of insulin-like growth-factor binding protein-2 (IGFBP-2) have been associated with increased adiposity and metabolic alterations such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease in individuals with obesity. However, whether IGFBP-2 affects energy metabolism in the early stages of these disorders remains unclear. Herein, we hypothesized that plasma IGFBP-2 concentrations are inversely associated with early liver fat accumulation and alterations in lipid and glucose homeostasis in apparently healthy and asymptomatic men and women. Three hundred thirty-three middle-aged Caucasian men and women apparently healthy and without cardiovascular symptoms were enrolled for a cross-sectional cardiometabolic imaging study. Individuals with BMI ≥ 40 kg/m2, cardiovascular disease, dyslipidemia, hypertension, and diabetes were excluded. Fasting glucose and lipid profiles were measured and an oral glucose tolerance test was performed. Liver fat content was assessed by magnetic resonance spectroscopy. Volume of visceral adipose tissue (VAT) was evaluated by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants with low IGFBP-2 levels were characterized by a higher body fat mass (P < 0.0001), insulin resistance (P < 0.0001), higher plasma triglyceride (TG) (P < 0.0001), and lower HDL-cholesterol levels (P < 0.0001) in a sex-independent manner. IGFBP-2 levels were inversely correlated with hepatic fat fraction in both men (r = -0.36, P < 0.0001) and women (r = -0.40, P < 0.0001). IGFBP-2 concentrations were negatively associated with hepatic fat fraction independently of age and VAT in both men (R2 = 0.23, P = 0.012) and women (R2 = 0.27, P = 0.028). In conclusion, our findings show that even in asymptomatic, apparently healthy individuals, low IGFBP-2 levels are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content in a VAT-independent manner. However, IGFBP-2 does not appear to influence the established sexual dimorphism observed for metabolic variables and hepatic fat fraction. Additional studies are required to better understand the relationships between IGFBP-2 and liver fat content.NEW & NOTEWORTHY Faced with a paucity of reliable clinical etiologic markers for fatty liver, this research article demonstrates, for the first time, that low blood levels of the protein IGFBP-2 are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content independently of visceral fat volume and sex, even in asymptomatic, apparently healthy individuals.

Overweight, Obesity, and CVD Risk: a Focus on Visceral/Ectopic Fat.

PURPOSE OF REVIEW: Despite its prevalence and well-documented impact on population health, obesity has not emerged as a strong independent risk factor for cardiovascular disease after control for intermediate risk factors. The purpose of this brief narrative review is to highlight results from imaging studies that have not only documented the remarkable heterogeneity of body fat topography but also the importance of visceral adiposity as a key body fat depot associated with cardiovascular disease risk and type 2 diabetes. RECENT FINDINGS: Simple tools are also discussed in order to refine cardiometabolic risk assessment in persons with overweight/obesity. It is proposed that four lifestyle vital signs should be considered in clinical practice to improve discrimination of health risk in individuals with overweight/obesity: waist circumference as a simple marker of abdominal adiposity, cardiorespiratory fitness, overall diet quality, and level of reported physical activity. Heterogeneity of obesity is proposed as an example of a condition that would benefit from a precision lifestyle medicine approach.

Visceral adiposity and liver fat as mediators of the association between cardiorespiratory fitness and plasma glucose-insulin homeostasis.

Cardiorespiratory fitness (CRF) is positively associated with insulin sensitivity, whereas excessive levels of visceral adipose tissue (AT) and liver fat (LF) are both associated with insulin resistance and impaired plasma glucose-insulin homeostasis. To what extent levels of visceral AT and LF content contribute to the relationship between CRF and indices of plasma glucose-insulin homeostasis is uncertain. Our objective was to explore the interactions among CRF, visceral AT, and LF with glucose tolerance/insulin levels in asymptomatic and apparently healthy individuals. CRF was measured in 135 women and 177 men with a maximal treadmill graded exercise test. Indices of plasma glucose-insulin homeostasis were derived from a 3-h oral glucose tolerance test (OGTT) performed in the morning after a 12-h fast. Visceral AT levels and LF content were measured using magnetic resonance imaging and spectroscopy. For any given CRF level, women presented significantly lower visceral AT and LF than men as well as lower homeostasis model assessment of insulin resistance (HOMA-IR) and plasma glucose-insulin levels during the OGTT compared with men. In both sexes, there were significant negative correlations between CRF and HOMA-IR as well as glucose and insulin levels measured during the OGTT. Both glucose and insulin levels during the OGTT correlated positively with visceral AT and LF. In women and men, being in the top CRF tertile was associated with low levels of visceral AT and LF. Multivariable linear regression analyses suggested that visceral AT and LF were plausible mediators of the association between CRF and indices of plasma glucose-insulin homeostasis.