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.

Dairy product intake and a person’s genetic background have been reported to be associated with the risk of type 2 diabetes (T2D). The objective of this study was to examine the interaction between dairy products and genes related to T2D on glucose-insulin homeostasis parameters. A validated food frequency questionnaire, fasting blood samples, and glucokinase (GCK) genotypes were analyzed in 210 healthy participants. An interaction between rs1799884 in GCK and dairy intake on the homeostasis model assessment of insulin resistance was identified. Secondly, human hepatocellular carcinoma cells (HepG2) were grown in a high-glucose medium and incubated with either 1-dairy proteins: whey, caseins, and a mixture of whey and casein; and 2-four amino acids (AA) or mixtures of AA. The expression of GCK-related genes insulin receptor substrate-1 (IRS-1) and fatty acid synthase (FASN) was increased with whey protein isolate or hydrolysate. Individually, leucine increased IRS-1 expression, whereas isoleucine and valine decreased FASN expression. A branched-chain AA mixture decreased IRS-1 and FASN expression. In conclusion, carriers of the A allele for rs1799884 in the GCK gene may benefit from a higher intake of dairy products to maintain optimal insulin sensitivity. Moreover, the results show that whey proteins affect the expression of genes related to glucose metabolism.

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.

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.

Excess liver fat (LF) is associated with low cardiorespiratory fitness (CRF), low physical activity, and a deteriorated cardiometabolic health profile including increased visceral adipose tissue (VAT). Whether the association between LF and CRF is mediated by visceral adiposity is unknown. We studied the contribution of VAT to the relationship between CRF and LF in asymptomatic women and men. The sample included 320 participants (43% women) who underwent LF quantification by magnetic resonance spectroscopy. VAT was measured by magnetic resonance imaging, CRF using maximal cardiorespiratory exercise testing, and moderate-to-vigorous intensity physical activity (MVPA) using a 3-day journal. Mean age was 50.3 ± 8.6 years, waist circumference was 89.3 ± 11.4 cm, and LF content was 4.3 ± 5.7%. LF was inversely correlated with CRF ( p < 0.0001), MVPA ( p < 0.05) and cardiometabolic health score ( p < 0.0001), and positively related with VAT ( p < 0.0001) in both sexes. Significantly higher levels of VAT ( p < 0.0001) and subcutaneous adipose tissue ( p < 0.0001) and a worsening cardiometabolic health score ( p < 0.05) and CRF ( p = 0.0001) were found across increasing sex-specific tertiles of LF levels. Lower levels of LF ( p < 0.01) and VAT ( p < 0.0001) and a higher cardiometabolic health score ( p < 0.0001) and MVPA ( p < 0.05) were noted across increasing sex-specific CRF tertiles. Multivariable regression analyses showed that visceral adiposity explained the majority of the variance in LF in both sexes ( p < 0.0001). Finally, serial mediation analyses revealed that VAT but not body fat percentage was a mediator in the relationship between CRF and LF in both sexes. Thus, visceral adiposity appears to be an important mediator in the relationship between CRF and LF, even after controlling for total adiposity.