Longitudinal associations between digital media use and ADHD symptoms in children and adolescents: a systematic literature review.

Previous reviews have often shown a link between digital media ADHD symptom levels. However, longitudinal studies are needed to find stronger evidence of a causal effect as well as to determine the direction of effects. The aim of the present review (PROSPERO CRD42021262695) was therefore to provide a systematic review of studies meeting the following inclusion criteria: (1) include longitudinal data investigating associations between digital media (i.e., gaming and social media) and later ADHD symptoms or vice versa, (2) be published within the past 10 years (i.e., 2011 until June 2021), (3) be published in a peer-reviewed journal in English, and (4) include children or adolescents (age 0-17 years). After a systematic search in the Web of Science and PsycInfo databases, we included 28 studies, all with adequate or high quality. Results showed support for reciprocal associations between digital media and ADHD symptoms, with associations being more consistent for problematic use of digital media than for screen time. Thus, children with ADHD symptoms appear more vulnerable to developing high or problematic use of digital media (i.e., selection effects), and digital media also have effects on later ADHD symptom levels, either because of specific characteristics of digital media or because of indirect effects on, for example, sleep and social relations (i.e., media effects). However, it should be emphasized that further studies investigating potential moderators and mediators are needed if we are to better understand the complex associations between digital media and ADHD symptom levels.

Gene expression and fiber type variations in repeated vastus lateralis biopsies.

INTRODUCTION: Muscle sample collection can introduce variation in any measured variable due to inter- and intramuscle variation. We investigated the variation in gene expression and fiber type composition after repeated biopsy sampling from the vastus lateralis muscle. METHODS: Six subjects donated 3 tissue samples each. One hour after baseline sampling from 1 vastus lateralis muscle, samples from both vastus lateralis muscles were obtained. RESULTS: The fiber type composition differed between biopsies taken from the same leg. There were no within-subject differences in gene expression between the 3 biopsies. Multivariate analysis supports a model in which gene expression differs significantly between individuals but is not affected by repeated muscle biopsy sampling from the same subject. CONCLUSION: One vastus lateralis muscle sample per subject is sufficient to establish a reliable baseline for comparing gene expression representing selected pathways over time within the same individual.

Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training.

PURPOSE: The effects of resistance training on mitochondrial biogenesis and oxidative capacity in skeletal muscle are not fully characterized, and even less is known about alterations in adipose tissue. We aimed to investigate adaptations in oxidative metabolism in skeletal muscle and adipose tissue after 8 weeks of heavy resistance training in apparently healthy young men. METHODS: Expression of genes linked to oxidative metabolism in the skeletal muscle and adipose tissue was assessed before and after the training program. Body composition, peak oxygen uptake (VO2 peak), fat oxidation, activity of mitochondrial enzyme in muscle, and serum adiponectin levels were also determined before and after resistance training. RESULTS: In muscle, the expression of the genes AdipoR1 and COX4 increased after resistance training (9 and 13 %, respectively), whereas the expression levels of the genes PGC-1α, SIRT1, TFAM, CPT1b, and FNDC5 did not change. In adipose tissue, the expression of the genes SIRT1 and CPT1b decreased after training (20 and 23 %, respectively). There was an increase in lean mass (from 59.7 ± 6.1 to 61.9 ± 6.2 kg), VO2 peak (from 49.7 ± 5.5 to 56.3 ± 5.0 ml/kg/min), and fat oxidation (from 6.8 ± 2.1 to 9.1 ± 2.7 mg/kg fat-free mass/min) after training, whereas serum adiponectin levels decreased significantly and enzyme activity of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase did not change. CONCLUSION: Despite significant increases in VO2 peak, fat oxidation, and lean mass following resistance training, the total effect on gene expression and enzyme activity linked to oxidative metabolism was moderate.

Effects of a Ketogenic Diet on Body Composition in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial.

This study investigates the effects of a ketogenic low-carbohydrate high-fat (LCHF) diet on body composition in healthy, young, normal-weight women. With the increasing interest in ketogenic diets for their various health benefits, this research aims to understand their impact on body composition, focusing on women who are often underrepresented in such studies. Conducting a randomized controlled feeding trial with a crossover design, this study compares a ketogenic LCHF diet to a Swedish National Food Agency (NFA)-recommended control diet over four weeks. Seventeen healthy, young, normal-weight women adhered strictly to the provided diets, with ketosis confirmed through blood ß-hydroxybutyrate concentrations. Dual-energy X-ray absorptiometry (DXA) was utilized for precise body composition measurements. To avoid bias, all statistical analyses were performed blind. The findings reveal that the ketogenic LCHF diet led to a significant reduction in both lean mass (-1.45 kg 95% CI: [-1.90;-1.00]; p < 0.001) and fat mass (-0.66 kg 95% CI: [-1.00;-0.32]; p < 0.001) compared to the control diet, despite similar energy intake and physical activity levels. This study concludes that while the ketogenic LCHF diet is effective for weight loss, it disproportionately reduces lean mass over fat mass, suggesting the need for concurrent strength training to mitigate muscle loss in women following this diet.

COVID-19 Restrictions Resulted in Both Positive and Negative Effects on Digital Media Use, Mental Health, and Lifestyle Habits.

While studies have reported effects on digital media during the COVID-19 restrictions, few have included data prior to the pandemic, and most have only measured screen time. We therefore investigated changes in specific digital media activities, as well as mental health and lifestyle habits, in a longitudinal study of adolescents spanning from before the pandemic (T1) to one month into restrictions (T2) and one year later when schools had reopened (T3). Adolescents (16-19 years) rated smartphone use, problematic/addictive media use, negative experiences (e.g., victimization), mental health (i.e., irritability, stress, and closeness), and protective lifestyle habits (i.e., sleep and exercise). Results showed initial decreases in irritability and negative digital experiences, increases in sleep and exercise, as well as a decrease in closeness during remote learning (T2). However, these changes returned to, or superseded, their initial levels at follow-up (T3). There were also increases in digital media use and stress at T3. Conclusively, by investigating specific digital media activities and collecting data both prior to and during different phases of the pandemic, we were able to find both positive and negative effects.

Screen time and addictive use of gaming and social media in relation to health outcomes.

Introduction: This study examined associations between screen time and addictive use (i.e., heavy involvement and negative consequences) of gaming and social media, and their independent effects on health outcomes. Methods: Survey data were collected from 2,265 participants (mean age = 21.57). Internet Gaming Disorder (IGD) and Social Media Disorder (SMD) were measured with the Gaming and Social Media Questionnaire (GSMQ-9), with separate measures for heavy involvement and negative consequences. Screen time was measured by weekly hours of gaming and social media. Assessed health outcomes were psychological problems, low self-concept, social problems, sleep problems, and sleep time. Results: Screen time and addictive use were significantly associated for both gaming and social media, with associations being stronger for symptoms of heavy involvement compared to symptoms of negative consequences. However, despite significant associations, a substantial proportion of the participants with a high screen time did not meet any or just one symptom of addiction. More importantly, it was primarily negative consequences that had independent effects on health outcomes, except for sleep. High levels of heavy involvement in gaming, were even related to lower, not higher, levels of psychological problems. Conclusion: The present findings study show that screen time is a poor indicator of addictive use of gaming and social media. Given that it was primarily negative consequences of gaming or social media that had effects on health outcomes, our study also emphasizes the need to distinguish between different types of addictive use and to further examine the diagnostic validity of the nine IGD symptom criteria.

The role of executive function deficits, delay aversion and emotion dysregulation in internet gaming disorder and social media disorder: Links to psychosocial outcomes.

Background and aims: It has been argued that it is important to consider underlying mechanisms of mental health problems. Previous studies have shown that executive deficits, delay aversion, and emotion dysregulation are related to Internet Gaming Disorder (IGD) and Social Media Disorder (SMD). However, the present study is the first to investigate whether these neuropsychological deficits show additive effects or if they interact. The present study also investigated whether these deficits mediate the association between IGD/SMD and psychosocial outcomes. Methods: The study involved 995 university students who completed a survey measuring IGD/SMD symptom severity, neuropsychological functions, and psychosocial outcomes. Both dimensional and categorical analyses were used to assess the associations between neuropsychological functions and IGD/SMD. Simple and multiple mediation analyses were conducted to examine if neuropsychological functioning mediates the association between IGD/SMD and psychosocial outcomes. Results: All neuropsychological functions were significantly associated with both IGD and SMD symptom severity. However, only inhibition and emotion regulation, as well as delay aversion for SMD, remained significant when controlling for the overlap between different functions. Associations were significantly stronger for men compared to women for IGD. In the categorical analyses, individuals with IGD/SMD were more likely to have neuropsychological deficits (odds ratios between 3.33 and 8.81). Finally, all neuropsychological functions, except inhibition, were significant mediators in the link between IGD/SMD and psychosocial outcomes. Discussion and conclusions: These results shed light on the neuropsychological underpinnings of IGD/SMD, which can be used to identify more homogenous subgroups and provide more individualized treatment options.

Adipose tissue IL-8 is increased in normal weight women after menopause and reduced after gastric bypass surgery in obese women.

OBJECTIVE: The menopausal transition is characterized by increased body fat accumulation, including redistribution from peripheral to central fat depots. This distribution is associated with an increased risk of type 2 diabetes and cardiovascular disease that are linked to low-grade inflammation. We determined whether postmenopausal women have higher levels of inflammatory markers, compared with premenopausal women. We also wanted to determine whether these markers are reduced by stable weight loss in obese women. DESIGN AND METHODS: Anthropometric data, blood samples and subcutaneous adipose tissue biopsies were collected from normal weight premenopausal and postmenopausal women and obese women before and 2 years after gastric bypass (GBP) surgery. Serum protein levels and adipose tissue gene expression of inflammatory markers were investigated. RESULTS: IL-8 expression in adipose tissue and circulating levels were higher in postmenopausal vs premenopausal women. IL-8 expression was associated with waist circumference, independent of menopausal status. IL-6 expression and serum levels of monocyte chemoattractant protein (MCP)-1 were higher in postmenopausal vs premenopausal women. Two years after GBP surgery, adipose expression of IL-8, tumour necrosis factor-α and MCP-1 decreased significantly. Serum insulin levels were associated with inflammation-related gene expression before GBP surgery, but these associations disappeared after surgery. CONCLUSION: Postmenopausal women have an increased inflammatory response in the subcutaneous fat and circulation. Inflammatory markers in adipose tissue decreased significantly after surgery-induced weight loss. This effect may be beneficial for metabolic control and reduced cardiovascular risk after weight loss.

Depot- and ethnic-specific differences in the relationship between adipose tissue inflammation and insulin sensitivity.

OBJECTIVE: It is unclear whether there are differences in inflammatory gene expression between abdominal and gluteal subcutaneous adipose tissue (SAT), and between black and white women. We therefore tested the hypotheses that SAT inflammatory gene expression is greater in the abdominal compared to the gluteal depot, and SAT inflammatory gene expression is associated with differential insulin sensitivity (S(I) ) in black and white women. DESIGN AND METHODS: S(I) (frequently sampled intravenous glucose tolerance test) and abdominal SAT and gluteal SAT gene expression levels of 13 inflammatory genes were measured in normal-weight (BMI 18-25 kg/m²) and obese (BMI >30 kg/m²) black (n = 30) and white (n = 26) South African women. RESULTS: Black women had higher abdominal and gluteal SAT expression of CCL2, CD68, TNF-α and CSF-1 compared to white women (P < 0·01). Multivariate analysis showed that inflammatory gene expression in the white women explained 56·8% of the variance in S(I) (P < 0·005), compared to 20·9% in black women (P = 0·30). Gluteal SAT had lower expression of adiponectin, but higher expression of inflammatory cytokines, macrophage markers and leptin than abdominal SAT depots (P < 0·05). CONCLUSIONS: Black South African women had higher inflammatory gene expression levels than white women; however, the relationship between AT inflammation and S(I) was stronger in white compared to black women. Further research is required to explore other factors affecting S(I) in black populations. Contrary to our original hypothesis, gluteal SAT had a greater inflammatory gene expression profile than abdominal SAT depots. The protective nature of gluteo-femoral fat therefore requires further investigation.

No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls.

UNLABELLED: BACKGROUND; Previous studies have indicated that peripheral circulating markers of inflammation are elevated in women with polycystic ovary syndrome (PCOS), but thus far no studies concerning markers of inflammation in adipose tissue have been published. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue. METHODS: Twenty overweight patients with PCOS, 10 lean patients with PCOS and 20 overweight controls had subcutaneous fat biopsies and blood samples taken. Adipose tissue levels of mRNA of inflammatory markers were determined by use of real-time PCR. RESULTS: Overweight patients with PCOS had higher relative adipose tissue chemokine ligand 2 (P < 0.01), and its cognate receptor (P < 0.05), tumour necrosis factor-α (P < 0.001), interleukin (IL)-10 (P < 0.001) and IL-18 (P < 0.001) and the monocyte/macrophage markers CD14 (P < 0.01) and CD163 (P < 0.01) mRNA levels compared with lean women with PCOS. There were no differences between overweight patients with PCOS and overweight control subjects in this respect. Within the PCOS group, markers of adipose tissue inflammation correlated significantly with obesity-related metabolic disturbances, but when data were adjusted for age and BMI, most correlations were lost. CONCLUSIONS: Overweight, rather than the PCOS diagnosis per se, appears to be the main explanatory variable for elevated adipose tissue inflammation in patients with PCOS.

A Ketogenic Low-Carbohydrate High-Fat Diet Increases LDL Cholesterol in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial.

Ketogenic low-carbohydrate high-fat (LCHF) diets are popular among young, healthy, normal-weight individuals for various reasons. We aimed to investigate the effect of a ketogenic LCHF diet on low-density lipoprotein (LDL) cholesterol (primary outcome), LDL cholesterol subfractions and conventional cardiovascular risk factors in the blood of healthy, young, and normal-weight women. The study was a randomized, controlled, feeding trial with crossover design. Twenty-four women were assigned to a 4 week ketogenic LCHF diet (4% carbohydrates; 77% fat; 19% protein) followed by a 4 week National Food Agency recommended control diet (44% carbohydrates; 33% fat; 19% protein), or the reverse sequence due to the crossover design. Treatment periods were separated by a 15 week washout period. Seventeen women completed the study and treatment effects were evaluated using mixed models. The LCHF diet increased LDL cholesterol in every woman with a treatment effect of 1.82 mM (p < 0.001). In addition, Apolipoprotein B-100 (ApoB), small, dense LDL cholesterol as well as large, buoyant LDL cholesterol increased (p < 0.001, p < 0.01, and p < 0.001, respectively). The data suggest that feeding healthy, young, normal-weight women a ketogenic LCHF diet induces a deleterious blood lipid profile. The elevated LDL cholesterol should be a cause for concern in young, healthy, normal-weight women following this kind of LCHF diet.

Reply to Ravnskov, U. Is High Cholesterol Deleterious? An Alternative Point of View. Comment on "Burén et al. A Ketogenic Low-Carbohydrate High-Fat Diet Increases LDL Cholesterol in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial. Nutrients 2021, 13, 814".

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Gaming and Social Media Addiction in University Students: Sex Differences, Suitability of Symptoms, and Association With Psychosocial Difficulties.

Background: Previous research has shown that addictions to digital media can have negative impact on psychosocial health. Although Internet Gaming Disorder (IGD) has received most scholarly recognition, the potential negative consequences of Social Media Disorder (SMD) have also been found. However, few studies have assessed the symptoms of these two digital media addictions in the same way, making comparisons difficult. The present study aims to fill this gap by investigating differences and similarities regarding how common the symptoms are, sex differences, the suitability of the symptoms, and their association with psychosocial difficulties. Method: A total of 688 university students (63.2% women, Mean age = 25.98) completed a questionnaire measuring symptoms of IGD and SMD, as well as psychosocial difficulties (i.e., psychosomatic symptoms, low self-concept, and social problems). Results: Results showed that 1.2% of the men and 0.9% of the women met the symptom criteria for IGD (non-significant difference), whereas 3.2% men and 2.8% women met the symptom criteria for SMD (non-significant difference). Dimensional analyses indicated that men had higher IGD scores compared to women, whereas the opposite was found for SMD. Symptoms of heavy involvement in digital media (i.e., Preoccupation, Tolerance, Withdrawal, Unsuccessful attempts to control, and Escape) had high sensitivity, but low positive predictive value (PPV). However, symptoms associated with negative consequences of digital media use (i.e., Loss of interest, Continued excessive use, Deception, and Jeopardizing career/relationships) had low sensitivity, but high PPV. These symptom patterns were similar for IGD and SMD. Meeting the criteria for IGD or SMD as well as being at risk of these disorders were significantly associated with psychosocial difficulties. Symptoms of SMD generally had stronger associations with psychosomatic symptoms compared to symptoms of IGD. Conclusions: We conclude that heavy involvement in digital media seems common among individuals with IGD or SMD, but also among those not meeting the symptom criteria, whereas negative consequences are less common but highly predictive of digital media addictions once present. Further attention to SMD is warranted, as it seems more common than IGD and also seems to be equally or more strongly associated with psychosocial difficulties.

Effects of a Ketogenic Diet on Muscle Fatigue in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial.

Ketogenic low-carbohydrate high-fat (LCHF) diets are increasingly popular in broad sections of the population. The main objective of this study was to evaluate the effects of a non-energy-restricted ketogenic LCHF diet on muscle fatigue in healthy, young, and normal-weight women. Twenty-four women were randomly allocated to a 4-week ketogenic LCHF diet followed by a 4-week control diet (a National Food Agency recommended diet), or the reverse sequence due to the crossover design. Treatment periods were separated by a 15 week washout period. Seventeen women completed the study and were included in the analyses. Treatment effects were evaluated using mixed models. The ketogenic LCHF diet had no effect on grip strength or time to fatigue, measured with handgrip test (day 24-26). However, cycling time to fatigue decreased with almost two minutes (-1.85 min 95% CI:[-2.30;-1.40]; p < 0.001) during incremental cycling (day 25-27), accommodated with higher ratings of perceived exertion using the Borg scale (p < 0.01). Participants' own diary notes revealed experiences of muscle fatigue during daily life activities, as well as during exercise. We conclude that in young and healthy women, a ketogenic LCHF diet has an unfavorable effect on muscle fatigue and might affect perceived exertion during daily life activities.

Hippocampal 11beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression has a diurnal variability that is lost in the obese Zucker rat.

Circulating levels of glucocorticoids show a circadian rhythm. Obesity is associated with a flattening of the diurnal rhythm; plasma cortisol levels are slightly increased during the trough, although they are normal or low in the morning. Studies in humans and in leptin-resistant Zucker rats suggest that tissue-specific alterations in glucocorticoid exposure might play a key role for development of obesity and obesity-associated dysregulation of the hypothalamic-pituitary-adrenal axis. We hypothesized that there is a circadian rhythm in prereceptor metabolism of glucocorticoids exerted by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in brain and/or peripheral tissues (liver, fat, and muscle) that might be abrogated in obesity. The present study demonstrates a circadian rhythm in 11beta-HSD1 mRNA expression (35-45% increase at morning vs. evening, P < 0.05) in dentate gyrus granular layer and CA1 subregions of the hippocampus in lean Zucker rats that was lost in the obese rats. Sprague Dawley rats also revealed a diurnal rhythm in hippocampal 11beta-HSD1 mRNA expression. There was no circadian variation in 11beta-HSD enzyme activity in peripheral tissues, although obese Zucker rats had a decreased enzyme activity in liver and epididymal fat (by approximately 40%, P < 0.05) compared with lean rats. In Sprague Dawley rats, 11beta-HSD activity in adipose tissue was higher in retroperitoneal and epididymal vs. sc fat (P < 0.001). In summary, obese Zucker rats lack a circadian rhythm of 11beta-HSD1 gene expression in the hippocampus, which may contribute to increased activity of the hypothalamic-pituitary-adrenal axis and altered diurnal variation of circulating corticosterone levels.

Insulin resistance induced by high glucose and high insulin precedes insulin receptor substrate 1 protein depletion in human adipocytes.

The aim of this study was to investigate whether high glucose and/or high insulin produces cellular insulin resistance in human adipocytes and, if so, to evaluate the time course and content of key proteins in the insulin signaling pathway. Subcutaneous fat biopsies were taken from 27 nondiabetic subjects. Insulin action in vitro was studied by measurement of glucose uptake after incubation at a physiologic glucose level (6 mmol/L) for 24 hours or with the last 2, 6, or 24 hours at a high glucose level (20 mmol/L) with or without high insulin (10(4)microU/mL). High glucose alone for 24 hours produced a small but significant impairment (by approximately 20%, P < .05) of insulin's effect to stimulate glucose transport, whereas nonstimulated glucose uptake was left intact. In contrast, the combination of high glucose and high insulin for 6 hours or more reduced basal glucose uptake by approximately 40% (P < .05). In addition, insulin-stimulated glucose uptake capacity was reduced by approximately 40% already after 2 hours (P < .05) and reached a maximal decline (by approximately 50%, P < .05) after a 6-hour culture in high glucose and high insulin. Treatment with high glucose and high insulin in combination for at least 6 hours reduced cellular insulin receptor substrate (IRS)-1, but not IRS-2, protein content by approximately 45% or more (P < .05). Moreover, after 24 hours, the ability of insulin to activate protein kinase B (ie, the phosphorylated protein kinase B [pPKB]-protein kinase B ratio) was decreased by approximately 50% (P < .05). No significant effects were seen on insulin signaling proteins or glucose transporter 4 after a long-term high-glucose culture. Culture with high insulin alone (and low glucose, 6 mmol/L) decreased basal and insulin-stimulated glucose uptake in conformity with the high-glucose/high-insulin setting. However, IRS-1 protein content remained unchanged. We conclude that, in adipocytes from healthy humans, high insulin alone for 2 hours or more decrease glucose uptake capacity. Likewise, high glucose and high insulin in combination for 2 hours or more decrease glucose uptake to the same extent as when cells were cultured with high insulin alone but, in addition, with a diminishment in IRS-1 protein lagging behind. Thus, IRS-1 depletion appears to be a secondary phenomenon in this model of insulin resistance. High glucose alone induces only a minor insulin resistance in human fat cells.

Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity.

OBJECTIVE: Abdominal fat accumulation after menopause is associated with low-grade inflammation and increased risk of metabolic disorders. Effective long-term lifestyle treatment is therefore needed. METHODS: Seventy healthy postmenopausal women (age 60 ± 5.6 years) with BMI 32.5 ± 5.5 were randomized to a Paleolithic-type diet (PD) or a prudent control diet (CD) for 24 months. Blood samples and fat biopsies were collected at baseline, 6 months, and 24 months to analyze inflammation-related parameters. RESULTS: Android fat decreased significantly more in the PD group (P = 0.009) during the first 6 months with weight maintenance at 24 months in both groups. Long-term significant effects (P < 0.001) on adipose gene expression were found for toll-like receptor 4 (decreased at 24 months) and macrophage migration inhibitory factor (increased at 24 months) in both groups. Serum interleukin 6 (IL-6) and tumor necrosis factor α levels were decreased at 24 months in both groups (P < 0.001) with a significant diet-by-time interaction for serum IL-6 (P = 0.022). High-sensitivity C-reactive protein was decreased in the PD group at 24 months (P = 0.001). CONCLUSIONS: A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation-related adipose gene expression.

A low-carbohydrate high-fat diet decreases lean mass and impairs cardiac function in pair-fed female C57BL/6J mice.

BACKGROUND: Excess body fat is a major health issue and a risk factor for the development of numerous chronic diseases. Low-carbohydrate diets like the Atkins Diet are popular for rapid weight loss, but the long-term consequences remain the subject of debate. The Scandinavian low-carbohydrate high-fat (LCHF) diet, which has been popular in Scandinavian countries for about a decade, has very low carbohydrate content (~5 E %) but is rich in fat and includes a high proportion of saturated fatty acids. Here we investigated the metabolic and physiological consequences of a diet with a macronutrient composition similar to the Scandinavian LCHF diet and its effects on the organs, tissues, and metabolism of weight stable mice. METHODS: Female C57BL/6J mice were iso-energetically pair-fed for 4 weeks with standard chow or a LCHF diet. We measured body composition using echo MRI and the aerobic capacity before and after 2 and 4 weeks on diet. Cardiac function was assessed by echocardiography before and after 4 weeks on diet. The metabolic rate was measured by indirect calorimetry the fourth week of the diet. Mice were sacrificed after 4 weeks and the organ weight, triglyceride levels, and blood chemistry were analyzed, and the expression of key ketogenic, metabolic, hormonal, and inflammation genes were measured in the heart, liver, and adipose tissue depots of the mice using real-time PCR. RESULTS: The increase in body weight of mice fed a LCHF diet was similar to that in controls. However, while control mice maintained their body composition throughout the study, LCHF mice gained fat mass at the expense of lean mass after 2 weeks. The LCHF diet increased cardiac triglyceride content, impaired cardiac function, and reduced aerobic capacity. It also induced pronounced alterations in gene expression and substrate metabolism, indicating a unique metabolic state. CONCLUSIONS: Pair-fed mice eating LCHF increased their percentage of body fat at the expense of lean mass already after 2 weeks, and after 4 weeks the function of the heart deteriorated. These findings highlight the urgent need to investigate the effects of a LCHF diet on health parameters in humans.

Insulin receptor substrates-1 and -2 are both depleted but via different mechanisms after down-regulation of glucose transport in rat adipocytes.

Alterations in muscle and adipose tissue insulin receptor substrate (IRS)-1 and IRS-2 are associated with, and commonly believed to contribute to, development of insulin resistance. In this study, we investigated the mechanisms behind previously observed reductions in IRS levels due to high concentrations of glucose and insulin and their significance in the impairment of glucose uptake capacity in primary rat adipocytes. Semiquantitative RT-PCR analysis showed that insulin (10(4) microU/ml) alone or in combination with glucose (15 mm) markedly suppressed IRS-2 gene expression, whereas IRS-1 mRNA was unaffected by the culture conditions. The negative effect of a high glucose/high insulin setting on IRS-1 protein level was still exerted when protein synthesis was inhibited with cycloheximide. Impairment of glucose uptake capacity after treatment with high glucose and insulin was most pronounced after 3 h, whereas IRS-1 and IRS-2 protein levels were unaffected up to 6 h but were reduced after 16 h. Moreover, impaired glucose uptake capacity could only partially be reversed by subsequent incubation at physiological conditions. These novel results suggest that: 1) in a high glucose/high insulin setting depletion of IRS-1 and IRS-2 protein, respectively, occurs via different mechanisms, and IRS-2 gene expression is suppressed, whereas IRS-1 depletion is due to posttranslational mechanisms; 2) IRS-1 and IRS-2 protein depletion is a secondary event in the development of insulin resistance in this model of hyperglycemia/hyperinsulinemia; and 3) depletion of cellular IRS in adipose tissue may be a consequence rather than a cause of insulin resistance and hyperinsulinemia in type 2 diabetes.

Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects.

BACKGROUND/AIM: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL). SUBJECTS AND METHODS: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin. RESULTS: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0+/-0.4 vs 2.0+/-0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by approximately 35-55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR. CONCLUSION: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.