Tissue-Specific Increases in 11β-Hydroxysteroid Dehydrogenase Type 1 in Normal Weight Postmenopausal Women

With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11βHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11βHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11βHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5α-tetrahydrocortisol+5β-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05), indicating an increased whole-body 11βHSD1 activity. Postmenopausal women had higher 11βHSD1 gene expression in subcutaneous fat (P<0.05). Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher hepatic 11βHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11βHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women

Neonatal Overfeeding Induced by Small Litter Rearing Causes Altered Glucocorticoid Metabolism in Rats

Elevated glucocorticoid (GC) activity may be involved in the development of the metabolic syndrome. Tissue GC exposure is determined by the tissue-specific GC-activating enzyme 11β-hydroxysteriod dehydrogenase type 1 (11β-HSD1) and the GC-inactivating enzyme 5α-reductase type 1 (5αR1), as well as 5β-reductase (5βR). Our aim was to study the effects of neonatal overfeeding induced by small litter rearing on the expression of GC-regulating enzymes in adipose tissue and/or liver and on obesity-related metabolic disturbances during development. Male Sprague-Dawley rat pup litters were adjusted to litter sizes of three (small litters, SL) or ten (normal litters, NL) on postnatal day 3 and then given standard chow from postnatal week 3 onward (W3). Small litter rearing induced obesity, hyperinsulinemia, and higher circulating corticosterone in adults. 11β-HSD1 expression and enzyme activity in retroperitoneal, but not in epididymal, adipose tissue increased with postnatal time and peaked at W5/W6 in both groups before declining. From W8, 11β-HSD1 expression and enzyme activity levels in retroperitoneal fat persisted at significantly higher levels in SL compared to NL rats. Hepatic 11β-HSD1 enzyme activity in SL rats was elevated from W3 to W16 compared to NL rats. Hepatic 5αR1 and 5βR expression was higher in SL compared to NL rats after weaning until W6, whereupon expression decreased in the SL rats and remained similar to that in NL rats. In conclusion, small litter rearing in rats induced peripheral tissue-specific alterations in 11β-HSD1 expression and activity and 5αR1 and 5βR expression during puberty, which could contribute to elevated tissue-specific GC exposure and aggravate the development of metabolic dysregulation in adults

Glucose and lipid metabolism in insulin resistance : an experimental study in fat cells

Type 2 diabetes is usually caused by a combination of pancreatic β-cell failure and insulin resistance in target tissues like liver, muscle and fat. Insulin resistance is characterised by an impaired effect of insulin to reduce hepatic glucose production and to promote glucose uptake in peripheral tissues. The focus of this study was to further elucidate cellular mechanisms for insulin resistance that may be of relevance for type 2 diabetes in humans. We used rat and human adipocytes as an established model of insulin’s target cells. Glucocorticoids, e.g. cortisol, can induce insulin resistance in vivo. In the present study, pretreatment of rat adipocytes in vitro for 24 h with the cortisol analogue dexamethasone produced a downregulation of glucose uptake capacity as well as a marked depletion of cellular insulin receptor substrate 1 (IRS-1) and protein kinase B (PKB), two proteins suggested to play a critical role in the intracellular signal transduction pathway of insulin. The amount of phosphorylated PKB in response to acute insulin treatment was decreased in parallel to total PKB content. The basal rate of lipolysis was enhanced, but insulin’s antilipolytic effect was not consistently altered following dexamethasone pretreatment. Alterations in blood glucose as well as insulin levels may be of great importance for cellular as well as whole-body insulin resistance. High glucose (≥15 mM) for 24 h induced a decrease in glucose uptake capacity in rat adipocytes and IRS-1 content was reduced whereas IRS-2 was increased. Long-term pretreatment with a high insulin concentration downregulated insulin binding capacity and when combined with high glucose, it produced a pronounced reduction of cellular IRS-1 and 2 content together with insensitivity to insulin’s effect to activate PKB and a decrease in glucose uptake capacity. A common denominator for a decrease in glucose uptake capacity in our rat adipocyte studies seems to be a decrease in IRS-1 content. Adipocytes from type 2 diabetes patients are insulin-resistant, but in our work the insulin resistance could be reversed by incubation of the cells at a physiological glucose level for 24 h. Insulin resistance in fresh adipocytes from type 2 diabetes patients was associated with in vivo insulin resistance and glycemic level and with adipocyte cell size and waist-hip ratio (WHR). As a potential mechanism for postprandial dyslipidemia in type 2 diabetes, we examined the nutritional regulation of subcutaneous adipose tissue lipoprotein lipase (LPL) activity. It was upregulated by ~40-50 % after a standardised lipid-enriched meal and this was very similar in type 2 diabetes patients and control subjects, suggesting that the postprandial hypertriglyceridemia found in type 2 diabetes is not explained by an altered nutritional regulation of LPL in subcutaneous fat. In conclusion, the present work provides evidence for novel interactions between glucocorticoids and insulin in the regulation of glucose metabolism that may potentially contribute to the development of insulin resistance. High levels of glucose and insulin produce perturbations in the insulin signalling pathway that may be of relevance for human type 2 diabetes. Cellular insulin resistance may be secondary to the diabetic state in vivo, e.g. via glucotoxicity. This is supported by our finding that insulin resistance in adipocytes from type 2 diabetes patients can be reversed after incubation at a physiological glucose level. Key words: adipocyte, insulin resistance, type 2 diabetes, insulin signalling, glucose uptake, insulin, glucose, dexamethasone, insulin receptor substrate, protein kinase B, GLUT4, lipoprotein lipase

Motionärer och elit har samma koll på kosten

Elitspelare i innebandyns superliga har inte bättre kunskap än motionärer om vilka kostrekommendationer som gäller vid träning. Lägst kunskap har spelarna om kostens betydelse för uppladdningen. För att kunna prestera maximalt är det viktigt att kunna anpassa energi-, närings- och vätskeintag till sin idrott

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”

We thank Ravnskov [...

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 sub-fractions and conventional cardiovascular risk factors in the blood of healthy, young, and nor-mal‐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% carbo-hydrates; 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 &lt; 0.001). In addition, Apolipoprotein B‐100 (ApoB), small, dense LDL cholesterol as well as large, buoyant LDL cholesterol increased (p &lt; 0.001, p &lt; 0.01, and p &lt; 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: Burén, J.; Ericsson, M.; Damasceno, N.R.T.; Sjödin, A. 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”. Nutrients 2021, 13, 2127. DOI: 10.3390/nu13072127</p

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 &lt; 0.001) during incremental cycling (day 25–27), accommodated with higher ratings of perceived exertion using the Borg scale (p &lt; 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

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