Approximately one-third of the U.S. population has nonalcoholic fatty liver disease (NAFLD), a condition closely associated with insulin resistance and increased risk of liver injury. Dysregulated ...mitochondrial metabolism is central in these disorders, but the manner and degree of dysregulation are disputed. This study tested whether humans with NAFLD have abnormal in vivo hepatic mitochondrial metabolism. Subjects with low (3.0%) and high (17%) intrahepatic triglyceride (IHTG) were studied using 2H and 13C tracers to evaluate systemic lipolysis, hepatic glucose production, and mitochondrial pathways (TCA cycle, anaplerosis, and ketogenesis). Individuals with NAFLD had 50% higher rates of lipolysis and 30% higher rates of gluconeogenesis. There was a positive correlation between IHTG content and both mitochondrial oxidative and anaplerotic fluxes. These data indicate that mitochondrial oxidative metabolism is ∼2-fold greater in those with NAFLD, providing a potential link between IHTG content, oxidative stress, and liver damage.
▸ Humans with nonalcoholic fatty liver disease (NAFLD) were identified by MRS ▸ Hepatic mitochondrial anaplerosis and gluconeogenesis were elevated during NAFLD ▸ Hepatic mitochondrial TCA cycle activity was doubled in subjects with NAFLD ▸ Elevated oxidative metabolism may predispose NAFLD patients to liver injury
In response to the COVID-19 pandemic, millions of students in China followed an emergency policy called "Suspending Classes without Stopping Learning" to continue their study online as schools across ...the country were closed. The present study examines how students adapted to learning online in these unprecedented circumstances. We aimed to explore the relationship between adaptability, academic emotion, and student engagement during COVID-19. 1,119 university students from 20 provinces participated in this longitudinal study (2 time points with a 2-week interval). The results showed that adaptability (the ability to respond to changes) and student engagement are significantly positively correlated with positive academic emotion and negatively correlated with negative academic emotion. Furthermore, adaptability not only directly predicts student engagement, but also affects student engagement through the chain mediation of positive academic emotion and negative academic emotion. The results contribute to the gap in knowledge regarding changes in students' learning in response to the outbreak. This study further explains the internal mechanisms mediating the relationship between adaptability and student engagement. It may provide references for educational researchers and universities in dampening the negative effects of COVID-19 on students' learning by improving their adaptability and developing positive academic emotions.
Student participation in online discussion forums is associated with positive outcomes for student achievement and satisfaction, but research findings on the impact of class size and instructors’ ...participation on student participation have been mixed. The present study analyzed the frequency of instructor and student posts in asynchronous discussion forums in 500 online courses to examine factors contributing to student participation. Results showed significant effects of both class size and amount of instructor participation, with a significant interaction between the two. In medium class sizes (with 15–30 students), amount of instructor participation did not predict the number of posts per student, but in smaller classes, significant differences in student participation were found depending on amount of instructor participation. Implications for fostering student participation in online discussion forums and interpreting research in this area are discussed.
Background and Aims
NAFLD and its more‐advanced form, steatohepatitis (NASH), is associated with obesity and is an independent risk factor for cardiovascular, liver‐related, and all‐cause mortality. ...Available human data examining hepatic mitochondrial fatty acid oxidation (FAO) and hepatic mitochondrial turnover in NAFLD and NASH are scant.
Approach and Results
To investigate this relationship, liver biopsies were obtained from patients with obesity undergoing bariatric surgery and data clustered into four groups based on hepatic histopathological classification: Control (CTRL; no disease); NAFL (steatosis only); Borderline‐NASH (steatosis with lobular inflammation or hepatocellular ballooning); and Definite‐NASH (D‐NASH; steatosis, lobular inflammation, and hepatocellular ballooning). Hepatic mitochondrial complete FAO to CO2 and the rate‐limiting enzyme in β‐oxidation (β‐hydroxyacyl‐CoA dehydrogenase activity) were reduced by ~40%–50% with D‐NASH compared with CTRL. This corresponded with increased hepatic mitochondrial reactive oxygen species production, as well as dramatic reductions in markers of mitochondrial biogenesis, autophagy, mitophagy, fission, and fusion in NAFL and NASH.
Conclusions
These findings suggest that compromised hepatic FAO and mitochondrial turnover are intimately linked to increasing NAFLD severity in patients with obesity.
Objective:
We aimed at determining the relationship of the gut microbiota and short chain fatty acids with obesity and fat partitioning and at testing potential differences in the ability of gut ...microbiota to ferment equal amounts of carbohydrates (CHO) between lean and obese youth.
Research Design and Methods:
We analyzed the gut microbiota of 84 youth in whom body fat distribution was measured by fast-magnetic resonance imaging, de novo lipogenesis (DNL) quantitated using deuterated water, and the capability of gut flora to ferment CHO was assessed by 13C-fructose treatment in vitro.
Results:
A significant association was found between the Firmicutes to Bacteroidetes ratio, and the abundance of Bacteroidetes and Actinobacteria with body mass index, visceral and SC fat (all P < .05). Plasma acetate, propionate, and butyrate were associated with body mass index and visceral and SC fat (all P < .05) and with hepatic DNL (P = .01, P = .09, P = .04, respectively). Moreover, the rate of CHO fermentation from the gut flora was higher in obese than in lean subjects (P = .018).
Conclusions:
These data demonstrate that obese youth show a different gut flora composition than lean and that short chain fatty acids are associated with body fat partitioning and DNL. Also, the gut microbiota of obese youth have a higher capability than the gut flora of lean to oxidize CHO.
We studied the association between gut microbiota and childhood obesity and observed that gut microbiota derived SCFA predispose to early onset obesity by enhancing hepatic de novo lipogenesis.
Background & Aims There have been few studies of the role of de novo lipogenesis in the development of nonalcoholic fatty liver disease (NAFLD). We used isotope analyses to compare de novo ...lipogenesis and fatty acid flux between subjects with NAFLD and those without, matched for metabolic factors (controls). Methods We studied subjects with metabolic syndrome and/or levels of alanine aminotransferase and aspartate aminotransferase >30 mU/L, using magnetic resonance spectroscopy to identify those with high levels (HighLF, n = 13) or low levels (LowLF, n = 11) of liver fat. Clinical and demographic information was collected from all participants, and insulin sensitivity was measured using the insulin-modified intravenous glucose tolerance test. Stable isotopes were administered and gas chromatography with mass spectrometry was used to analyze free (nonesterified) fatty acid (FFA) and triacylglycerol flux and lipogenesis. Results Subjects with HighLF (18.4% ± 3.6%) had higher plasma levels of FFAs during the nighttime and higher concentrations of insulin than subjects with LowLF (3.1% ± 2.7%; P = .04 and P < .001, respectively). No differences were observed between groups in adipose flux of FFAs (414 ± 195 μmol/min for HighLF vs 358 ± 105 μmol/min for LowLF; P = .41) or production of very-low-density lipoprotein triacylglycerol from FFAs (4.06 ± 2.57 μmol/min vs 4.34 ± 1.82 μmol/min; P = .77). In contrast, subjects with HighLF had more than 3-fold higher rates of de novo fatty acid synthesis than subjects with LowLF (2.57 ± 1.53 μmol/min vs 0.78 ± 0.42 μmol/min; P = .001). As a percentage of triacylglycerol palmitate, de novo lipogenesis was 2-fold higher in subjects with HighLF (23.2% ± 7.9% vs 10.1% ± 6.7%; P < .001); this level was independently associated with the level of intrahepatic triacylglycerol ( r = 0.53; P = .007). Conclusions By administering isotopes to subjects with NAFLD and control subjects, we confirmed that those with NAFLD have increased synthesis of fatty acids. Subjects with NAFLD also had higher nocturnal plasma levels of FFAs and did not suppress the contribution from de novo lipogenesis on fasting. These findings indicate that lipogenesis might be a therapeutic target for NAFLD.
Successful everyday self-regulation often hinges on implementing intended responses at a later time-often in specific situations. We address this self-regulation challenge by examining the role of ...individuals' thought about intended actions-and specifically whether it does or does not include situational cues. We hypothesized that including situational cues when thinking about intended actions enables stimulus-response learning, thereby increasing the likelihood of implementing the intended actions. Consequently, we pre-registered and found (N = 392, age range 18-94) a positive relationship between the self-reported habitual inclusion of situational cues in thought about intended actions and everyday self-regulation success (assessed by self-reported self-efficacy and self-control beliefs). In addition, we provide exploratory evidence that the inclusion of situational cues in thought about intended actions mediates the relationship between conscientiousness and self-regulation success. We discuss the results and the theoretical perspective in relation to how self-control outcomes can be explained by associative learning.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Biochemical evidence has linked the coordinate control of fatty acid (FA) synthesis with the activity of stearoyl-CoA desaturase-1 (SCD1). The ratio of 16:1n–7 to 16:0 SCD1(16) in plasma ...triacylglycerol FA has been used as an index to reflect liver SCD1(16) activity and has been proposed as a biomarker of FA synthesis, although this use has not been validated by comparison with isotopically measured de novo lipogenesis (DNLMeas).Objective: We investigated plasma lipid 16:1n–7 and FA indexes of elongation and desaturation in relation to lipogenesis.Design: In this cross-sectional investigation of metabolism, 24 overweight adults, who were likely to have elevated DNL, consumed D2O for 10 d and had liver fat (LF) measured by magnetic resonance spectroscopy. Very-low-density lipoprotein (VLDL)-triacylglycerols and plasma free FA nonesterified fatty acids (NEFAs) were analyzed by using gas chromatography for the FA composition (molar percentage) and gas chromatography–mass spectrometry and gas chromatography–combustion isotope ratio mass spectrometry for deuterium enrichment.Results: In all subjects, VLDL-triacylglycerol 16:1n–7 was significantly (P < 0.01) related to DNLMeas (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD1(16) index, and the pattern in NEFAs echoed that of VLDL-triacylglycerols. Compared with subjects with low LF (3.1 ± 2.7%; n = 11), subjects with high LF (18.4 ± 3.6%; n = 13) exhibited a 45% higher VLDL-triacylglycerol 16:1n–7 molar percentage (P < 0.01), 16% of subjects had lower 18:2n–6 (P = 0.01), and 27% of subjects had higher DNL as assessed by using a published DNL index (ratio of 16:0 to 18:2n–6; P = 0.03), which was isotopically confirmed by DNLMeas (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n–7 in VLDL-triacylglycerols corresponded to a stronger signal of elevated DNL.Conclusion: The current data provide support for the use of the VLDL-triacylglycerol 16:1n–7 molar percentage as a biomarker for elevated liver fat when isotope use is not feasible; however, larger-scale confirmatory studies are needed. This trial was registered at clinicaltrials.gov as NCT01371396.
The COVID‐19 pandemic had negative effects on many people's well‐being and quality of life. In the present work, we focused on Norwegian mothers with elementary school children, and investigated ...whether their well‐being, stress, and worries (and the relationships between them) changed across the early months of the pandemic. We collected data at two time points in 2020. In June 2020, 231 mothers (mean age = 40.09, SD = 6.22) responded to an online questionnaire in which they were asked to indicate their well‐being, stress, and worries before the pandemic, during the lockdown (i.e., March 2020), and currently (i.e., June 2020). Of these 231 mothers, 97 (mean age = 40.58, SD = 5.66) answered the same questionnaire again in November 2020. Mothers' well‐being was lower in November 2020 than before the pandemic (retrospectively reported). The age of the youngest child showed the strongest and most consistent relationship with mothers' well‐being across all time points. In addition, we found that the stress mothers felt during the national lockdown in March 2020 was strongly associated with their well‐being both during the lockdown and in June 2020. Finally, in November 2020, mothers' financial pandemic‐related worries were negatively related to their well‐being. Implications and suggestions for future research and for how societies can cope with future health‐related crises are discussed.
As parental leave policies increasingly encourage new fathers to take paternal leave, the present experimental study explores evaluations of male and female workers who do (or do not) complete ...work‐related tasks during leave. In line with our preregistered hypotheses, not completing work‐related tasks during leave resulted in costs for men's (but not women's) evaluations and recommendations, whereas working during leave benefited women's (but not men's) evaluations and recommendations. Parallel evaluations of workers' agency suggest prescriptive gender norms underlie these different responses to men's and women's behaviour.
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