Peripheral inflammation associated with depression and reduced weight loss: a longitudinal study of bariatric patients.

BACKGROUND: Research implicates inflammation in the vicious cycle between depression and obesity, yet few longitudinal studies exist. The rapid weight loss induced by bariatric surgery is known to improve depressive symptoms dramatically, but preoperative depression diagnosis may also increase the risk for poor weight loss. Therefore, we investigated longitudinal associations between depression and inflammatory markers and their effect on weight loss and clinical outcomes in bariatric patients. METHODS: This longitudinal observational study of 85 patients with obesity undergoing bariatric surgery included 41 cases with depression and 44 controls. Before and 6 months after surgery, we assessed depression by clinical interview and measured serum high-sensitivity C-reactive protein (hsCRP) and inflammatory cytokines, including interleukin (IL)-6 and IL-10. RESULTS: Before surgery, depression diagnosis was associated with significantly higher serum hsCRP, IL-6, and IL-6/10 ratio levels after controlling for confounders. Six months after surgery, patients with pre-existing depression still had significantly higher inflammation despite demonstrating similar weight loss to controls. Hierarchical regression showed higher baseline hsCRP levels predicted poorer weight loss (ß = -0.28, p = 0.01) but had no effect on depression severity at follow-up (ß = -0.02, p = 0.9). Instead, more severe baseline depressive symptoms and childhood emotional abuse predicted greater depression severity after surgery (ß = 0.81, p < 0.001; and ß = 0.31, p = 0.001, respectively). CONCLUSIONS: Depression was significantly associated with higher inflammation beyond the effect of obesity and other confounders. Higher inflammation at baseline predicted poorer weight loss 6 months after surgery, regardless of depression diagnosis. Increased inflammation, rather than depression, may drive poor weight loss outcomes among bariatric patients.

Disentangling the effects of depression and perceived stress on cortisol levels in individuals with obesity: Preliminary results from a cross-sectional study.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been suggested to play a role in the association between depression and obesity. The study aimed to investigate differences in cortisol levels in individuals with obesity with and without depression and the role of perceived stress on these differences. METHODS: Saliva samples were collected at awakening, 15-, 30- and 60-minutes post-awakening from 66 individuals with obesity (30 with major depressive disorder and 36 without major depressive disorder). Salivary cortisol was analysed using ELISA technique. Linear Mixed Models were used for group differences in cortisol awakening response (CAR) with adjustment for socio-demographic confounders and binge eating. RESULTS: Individuals with obesity and depression had lower CAR compared with individuals with obesity without depression (ß = -0.44; p = 0.036). When controlling for perceived stress, CAR was no longer influenced by depression (ß = -0.09; p = 0.75), but individuals with moderate/high stress had lower CAR compared with those with low stress (ß = -0.63; p = 0.036). CONCLUSIONS: Our results suggest that differences in CAR between individuals with obesity with and without depression could be due to higher levels of perceived stress in the depressed subjects.

Fear conditioning in women with anorexia nervosa and healthy controls: A preliminary study.

Anorexia nervosa is characterized by anxiety-driven behaviors, such as food avoidance and distressing persistent thoughts about weight gain and body image. The present study used a classical fear conditioning procedure to test the processes of fear acquisition and generalization, extinction, and renewal in patients with anorexia nervosa and healthy controls. An app-based fear conditioning procedure was administered remotely to 64 patients and 60 healthy controls, over two sessions. A human female scream served as the unconditioned stimulus (US) and two neutral shapes were used as either the paired conditioned stimulus (danger cue; CS+) or the unpaired conditioned stimulus (safe cue; CS-). Patients with anorexia nervosa reported greater threat expectancy in response to the danger cue during the extinction and renewal phases and overall higher levels of negative affect throughout the task, compared with controls. Future research is warranted to replicate these findings and highlight the role that anxiety plays in explaining fear conditioning responses in patients with anorexia nervosa. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Lower pattern recognition memory scores in anorexia nervosa.

BACKGROUND: There is extensive evidence for volumetric reductions in the hippocampus in patients with anorexia nervosa (AN), however the impact on function is unclear. Pattern separation and recognition are hippocampus-dependent forms of learning thought to underlie stimulus discrimination. METHODS: The present study used the Mnemonic Similarity Task to investigate pattern separation and recognition for the first time in patients with AN (N = 46) and healthy controls (N = 56). An Analysis of Covariance examined between-group differences, controlling for age, antidepressant use and method of task delivery (remote vs. in person). RESULTS: When controlling for covariates, pattern recognition memory scores were lower in the AN group with a medium effect size (d = 0.51). In contrast, there was a small effect whereby patients with AN had a greater pattern separation score than controls (d = 0.34), albeit this difference was not significant at the p = 0.05 threshold (p = 0.133). Furthermore, pattern separation and recognition memory abilities were not related to age, body mass index, eating disorder psychopathology or trait anxiety levels. CONCLUSIONS: This preliminary study provides initial evidence for an imbalance in pattern separation and recognition abilities in AN, a hippocampus-dependent cognitive ability. Further studies should endeavour to investigate pattern separation and recognition performance further in AN, as well as investigate other hippocampus-dependent functions.

The hippocampus is an area of the brain that is vital for memory and learning, and it is not understood the extent to which its function is impaired in anorexia nervosa (AN). This paper used the Mnemonic Similarity Task to assess pattern separation, a hippocampus-dependent form of memory, in AN. This task involves showing participants a sequence of objects, who then categorise them as "indoor" or "outdoor" objects. Participants are later shown a sequence of objects, although some of the images are replaced by a similar but slightly different image. The task involves recognising whether an image has previously been seen (pattern recognition) and also whether it is similar to, but distinct, from a previous image (i.e. pattern separation). In this study, individuals with AN showed reduced performance in pattern recognition, when statistically controlling for their age, how the task was delivered and their use of antidepressant medication. However, their performance in pattern separation was intact. This may indicate an imbalance in this hippocampus-dependent form of memory in AN.

Effects of weight stigma in news media on physical activity, dietary and weight loss intentions and behaviour.

OBJECTIVES: To investigate the effect of weight stigma in news media on (a) intentions to increase physical activity (PA), improve diet quality and lose weight, and (b) changes in PA, diet quality and body mass index (BMI) over one month, in (i) women of all weight categories and (ii) a subsample of women living with obesity. METHODS: UK-based women (N=172; subgroup with obesity N=81) were assigned to read an experimental (weight stigma; N=75) or control (smoking stigma; N=97) news article. Questionnaires were administered immediately after, and one month subsequently to collect information on BMI, PA, diet quality, intentions, past stigma, and diet and PA self-efficacy. Logistic and linear regression analyses were used to assess the effect of weight stigma on all outcome variables. RESULTS: In the whole sample, there was no significant effect of weight stigma on any primary or secondary outcome. In women with obesity, there was no significant effect of weight stigma on diet quality (0.26 units, 95% CI: -0.36 to 0.87) or PA (-1.83 units, 95% CI: -11.11 to 7.44) at follow up, but exposure to weight stigma was associated with a significant increase in BMI at 1-month follow-up (1.15kg/m2, 95% CI: 0.38 to 1.92) compared with the control group. CONCLUSIONS: In people with obesity, exposure to weight-stigmatising media may contribute to increased BMI over time. Larger trials with longer follow-up are needed to confirm these findings.

Modulation of triterpene saponin production: in vitro cultures, elicitation, and metabolic engineering.

Saponins are secondary metabolites that are widely distributed in the plant kingdom and are often the active components in medicinal herbs. Hence, saponins have a potential for the pharmaceutical industry as antibacterial, virucidal, anti-inflammatory, and anti-leishmanial drugs. However, their commercial application is often hindered because of practical problems, such as low and variable yields and limited availability of natural resources. In vitro cultures provide an alternative to avoid problems associated with field production; they offer a system in which plants are clonally propagated and yield is not affected by environmental changes. Additionally, treatment of in vitro cultures with elicitors such as methyl jasmonate may increase the production of saponins up to six times. In vitro cultures are amenable to metabolic engineering by targeting specific genes to enhance saponin production or drive production towards one specific class of saponins. Hitherto, this approach is not yet fully explored because only a limited number of saponin biosynthesis genes are identified. In this paper, we review recent studies on in vitro cultures of saponin-producing plants. The effect of elicitation on saponin production and saponin biosynthesis genes is discussed. Finally, recent research efforts on metabolic engineering of saponins will also be presented.

alpha-Skeletal muscle actin nemaline myopathy mutants cause cell death in cultured muscle cells.

Nemaline myopathy is a neuromuscular disorder, characterized by muscle weakness and hypotonia and is, in 20% of the cases, caused by mutations in the gene encoding alpha-skeletal muscle actin, ACTA1. It is a heterogeneous disease with various clinical phenotypes and severities. In patients the ultrastructure of muscle cells is often disturbed by nemaline rods and it is thought this is the cause for muscle weakness. To search for possible defects during muscle cell differentiation we expressed alpha-actin mutants in myoblasts and allowed these cells to differentiate into myotubes. Surprisingly, we observed two striking new phenotypes in differentiating myoblasts: rounding up of cells and bleb formation, two features reminiscent of apoptosis. Indeed expression of these mutants induced cell death with apoptotic features in muscle cell culture, using AIF and endonuclease G, in a caspase-independent but calpain-dependent pathway. This is the first report on a common cellular defect induced by NM causing actin mutants, independent of their biochemical phenotypes or rod and aggregate formation capacity. These data suggest that lack of type II fibers or atrophy observed in nemaline myopathy patients may be also due to an increased number of dying muscle cells.

Phenotypes induced by NM causing alpha-skeletal muscle actin mutants in fibroblasts, Sol 8 myoblasts and myotubes.

BACKGROUND: Nemaline myopathy is a neuromuscular disorder characterized by the presence of nemaline bodies in patient muscles. 20% of the cases are associated with alpha-skeletal muscle actin mutations. We previously showed that actin mutations can cause four different biochemical phenotypes and that expression of NM associated actin mutants in fibroblasts, myoblasts and myotubes induces a range of cellular defects. FINDINGS: We conducted the same biochemical experiments for twelve new actin mutants associated with nemaline myopathy. We observed folding and polymerization defects. Immunostainings of these and eight other mutants in transfected cells revealed typical cellular defects such as nemaline rods or aggregates, decreased incorporation in F-actin structures, membrane blebbing, the formation of thickened actin fibres and cell membrane blebbing in myotubes. CONCLUSION: Our results confirm that NM associated alpha-actin mutations induce a range of defects at the biochemical level as well as in cultured fibroblasts and muscle cells.

alpha-Skeletal muscle actin mutants causing different congenital myopathies induce similar cytoskeletal defects in cell line cultures.

Central core disease (CCD), congenital fibre type disproportion (CFTD), and nemaline myopathy (NM) are earlyonset clinically heterogeneous congenital myopathies, characterized by generalized muscle weakness and hypotonia. All three diseases are associated with alpha-skeletal muscle actin mutations. We biochemically characterized the CCD and CFTD causing actin mutants and show that all mutants fold correctly and are stable. Expression studies in fibroblasts, myoblasts, and myotubes show that these mutants incorporate in filamentous structures. However they do not intercalate between the nascent z-lines in differentiating muscle cell cultures. We also show that the distribution of mitochondria and of the ryanodine receptors, and calcium release properties from ryanodine receptors, are unchanged in myotubes expressing the CCD causing mutants. CFTD causing mutants induce partly similar phenotypes as NM associated ones, such as rods and thickened actin fibers in cell culture. Our results suggest that molecular mechanisms behind CFTD and NM may be partly related.