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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. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the clinical safety, tolerability, and pharmacokinetic and pharmacodynamic profile of the novel cannabinoid receptor‐1 (CB1R) inverse agonist, INV‐202, in adults with features of metabolic syndrome. Materials and Methods: This was a multicentre, randomized, double‐blind, placebo‐controlled, 28‐day repeat‐dose (INV‐202 [25 mg] or placebo, once‐daily oral tablet), parallel‐group study in 37 participants aged 18 to 65 years (46% female, mean age 55 years, glycated haemoglobin 5.7% [39 mmol/mol], body mass index [BMI] 38.1 kg/m2) with features of metabolic syndrome and glucose intolerance. An oral glucose tolerance test (OGTT) was performed at baseline and at the end of the study. Lipid profiles, weight, waist circumference and biomarkers were assessed weekly. Statistical comparisons were performed post hoc. Results: INV‐202 was well tolerated with no serious or severe treatment‐emergent adverse events; the most common events related to known effects of CB1R blockade in the gastrointestinal tract. INV‐202 produced a significant mean weight loss of 3.5 kg (3.3% compared with placebo participants who gained a mean 0.6 kg [0.5%]). INV‐202 also exhibited significant reductions in waist circumference and BMI (P ≤ 0.03). There was no significant difference in OGTT 0‐ to 3‐hour area under the curve for INV‐202 versus placebo: least squares mean 29.38 versus 30.25 h*mmol/L, with an INV‐202: placebo ratio of 97.1% (95% confidence interval 90.2, 105.6; P = 0.43). Conclusions: INV‐202 was well tolerated, producing a signal for rapid weight loss with improvements in other metabolic syndrome markers in this population. These findings support further exploration and long‐term assessment of cardiometabolic effects. [ABSTRACT FROM AUTHOR]

Dr. Denis Richard, a renowned physiologist, passed away in December 2023, leaving a significant impact on academia and those who knew him. He received his Ph.D. in Physiology from Université Laval in 1982 and made important contributions to the field of the central control of energy balance. Dr. Richard was a pioneer in the neurobiology of obesity and focused on understanding the role of the central nervous system in regulating metabolism. He organized numerous international symposia and was known for his mentorship and visionary leadership. His legacy will continue to influence the fields of physiology and neuroendocrinology. [Extracted from the article]

This cardiometabolic imaging study was designed to document the adaptation of middle-aged recreational cyclists to a large exercise prescription not aiming at weight loss. Eleven middle-aged recreational male cyclists traveled 1,144 km over seven consecutive days. A comprehensive cardiometabolic profile including visceral and ectopic adiposity assessed by magnetic resonance imaging was obtained at baseline and following the exercise week. Cardiorespiratory fitness (CRF) was measured using maximal cardiopulmonary exercise testing. During the week, heart rate was monitored to calculate individual energy expenditure. Baseline characteristics of cyclists were compared with 86 healthy males in the same age range. Cyclists presented higher baseline CRF (+9.2 mL/kg/min, P < 0.0001) and lower subcutaneous (-56.2 mL, P < 0.05) and liver (-3.3%, P < 0.05) fat compared with the reference group. Despite the large energy expenditure during the cycling week, the increase in energy intake limited decreases in body weight (-0.8 ± 0.9 kg, P < 0.05) and body mass index (-0.3 ± 0.3 kg/m 2 , P < 0.05). Loss of fat mass (-1.5 ± 1.0 kg, P < 0.001) and a trend toward an increased lean mass (+0.8 ± 1.2 kg, P < 0.07) were observed. Visceral adiposity (-14.1 ± 14.2 mL, P < 0.01) and waist circumference (-3.2 ± 1.7 cm, P < 0.0001) decreased, whereas subcutaneous (-2.7 ± 5.1 mL, NS), liver (-0.5 ± 0.9%, NS), and cardiac (-0.3 ± 2.3 mL, NS) fat remained unchanged. This cardiometabolic imaging study documents middle-aged recreational cyclists' subcutaneous and visceral adiposity as well as cardiac and liver fat responses to a large volume of endurance exercise despite an increase in energy intake aimed at limiting weight loss. NEW & NOTEWORTHY Even when being accompanied by a substantial increase in energy intake to compensate energy expenditure and limit weight loss, a large volume of endurance exercise performed within a short period of time is associated with a significant reduction in visceral adiposity. High cardiorespiratory fitness is associated with low levels of liver fat in middle-aged males.

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/m 2 , 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 ( R 2  = 0.23, P = 0.012) and women ( R 2  = 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.