Pathophysiological mechanisms that alter the autonomic brain-liver communication in metabolic diseases

The brain influences liver metabolism through many neuroendocrine and autonomic mechanisms that have evolved to protect the organism against starvation and hypoglycemia. Unfortunately, what is normally an effective way to prevent death has become dysregulated in modern obesogenic environments, but the pathophysiological mechanisms behind metabolic dyshomeostasis are still unclear. In this Mini-Review, we provide our thoughts regarding obesity and type 2 diabetes as diseases of the autonomic nervous system. We discuss the pathophysiological mechanisms that alter the autonomic brain-liver communication in these diseases, and how they could represent important targets to prevent or treat metabolic dysfunctions. We discuss how sympathetic hyperactivity to the liver may represent an early event in the progression of metabolic diseases and could progressively lead to hepatic neuropathy. We hope that this discussion will inspire and help framing a model on the importance of better understanding the chronology of autonomic dysfunctions in the liver in order to apply the right strategy at the right time.

Obesogenic Environments in the Middle-Aged Korean Men: Based on 2020 KDRIs

Objectives According to 2019 KNHANES, the obesity prevalence of Korean adults was 33.8% and it has been increased by 2.5% in the past decade. With the highest prevalence of men aged 30–40 years old as 45–46.4%, we aimed to find what environmental variables affect the obesity prevalence in the middle-aged man. Methods Using the 7th KNHANES (2016–2018), obesogenic environments, such as nutrients intakes, dietary habits, lifestyle habits/disease, and exercise were collected/analyzed to elucidate the causality of obesity in 907 middle-aged men. Using the nutrient levels of 2015 and 2020 Korean Dietary Reference Intake (KDRIs) recommendation, we figured out what the variables, such as nutrients over/under intakes, lifestyle changes, dietary habits, were involved in obesogenic environments in 30–40 aged men. Results In men aged 30–40 years old, protein (146.2%) and sodium (198%) intakes were increased, however, dietary intakes of Vit A (75%) decreased, although their DRI values were elevated in 2020 KDRIs compared to 2015. Calcium (74.9%) and Vit C (72.5%), phosphate (190.7%), iron (149.7%), thiamine (141.6%), riboflavin (134.0%), and niacin (111.5%) should be fit for middle-aged men as much as each value of 2020 KDRIs recommendation. The rate of breakfast skipping was 48.1% in the thirties and 37.9% in forties, and eating out frequency was highest in 30–40 as 50%. Moreover, the drinking rate was 80.8% in the thirties as 1st, 74.9% in forties as 2nd, and the rate of muscle exercise practice in men aged 30–40 years was lower than fifties, the rate of stress cognition was highest in thirties (38.8%) in the whole lifestyle. Conclusions It is easy to neglect health and nutrition management in middle-aged men between 30 and 40 because that age is the most active on economics during life. Based on our results, we recommend the nutritional management or education in the workplace of middle-aged men and personalized diets to prevent chronic diseases in the coming elderly stage. Funding Sources This work was supported by the Rural Development Administration of Korea (RDA) grant funded by the Korea government.

Lifetime risk of diabetes in metropolitan cities in India

Aims/hypothesis We aimed to estimate the lifetime risk of diabetes and diabetes-free life expectancy in metropolitan cities in India among the population aged 20 years or more, and their variation by sex, age and BMI. Methods A Markov simulation model was adopted to estimate age-, sex- and BMI-specific lifetime risk of developing diabetes and diabetes-free life expectancy. The main data inputs used were as follows: age-, sex- and BMI-specific incidence rates of diabetes in urban India taken from the Centre for Cardiometabolic Risk Reduction in South Asia (2010–2018); age-, sex- and urban-specific rates of mortality from period lifetables reported by the Government of India (2014); and prevalence of diabetes from the Indian Council for Medical Research INdia DIABetes study (2008–2015). Results Lifetime risk (95% CI) of diabetes in 20-year-old men and women was 55.5 (51.6, 59.7)% and 64.6 (60.0, 69.5)%, respectively. Women generally had a higher lifetime risk across the lifespan. Remaining lifetime risk (95% CI) declined with age to 37.7 (30.1, 46.7)% at age 60 years among women and 27.5 (23.1, 32.4)% in men. Lifetime risk (95% CI) was highest among obese Indians: 86.0 (76.6, 91.5)% among 20-year-old women and 86.9 (75.4, 93.8)% among men. We identified considerably higher diabetes-free life expectancy at lower levels of BMI. Conclusions/interpretation Lifetime risk of diabetes in metropolitan cities in India is alarming across the spectrum of weight and rises dramatically with higher BMI. Prevention of diabetes among metropolitan Indians of all ages is an urgent national priority, particularly given the rapid increase in urban obesogenic environments across the country.

Development and evaluation of a digital, community-based intervention to reduce noncommunicable disease risk in a low-resource urban setting in Malaysia: a research protocol

Background Noncommunicable disease burden is rising in Malaysia, accounting for 72% of all deaths. Urbanization and globalization have contributed to changing patterns of diet and physical activity, creating an obesogenic environment that increases noncommunicable disease risk, especially in low-income populations. Community-based and technological interventions can play an important role in addressing structural determinants that influence noncommunicable disease burden. The Better Health Programme Malaysia aims to co-create and develop a community-based digital intervention for low-income populations to enable community stakeholders to address obesogenic environments and improve people’s knowledge, attitudes, and practices related to noncommunicable disease risk. Methods This quasi-experimental study will assess community member and community health volunteer knowledge, attitudes, and practices on noncommunicable disease prevention, risk factors, and health-seeking behavior in three geographical areas of Kuala Lumpur, each representing a different ethnicity (Malay, Indian, and Chinese). Assessment will take place before and after a 9-month intervention period, comparing intervention areas with matched control geographies. We plan to engage 2880 community members and 45 community health volunteers across the six geographic areas. A digital health needs assessment will inform modification of digital health tools to support project aims. Intervention co-creation will use a discrete choice experiment to identify community preferences among evidence-based intervention options, building from data collected on community knowledge, attitudes, and practices. Community health volunteers will work with local businesses and other stakeholders to effect change in obesogenic environments and NCD risk. The study has been approved by the Malaysian Ministry of Health Medical Research Ethical Committee. Discussion The Better Health Programme Malaysia anticipates a bottom-up approach that relies on community health volunteers collaborating with local businesses to implement activities that address obesogenic environments and improve community knowledge, attitudes, and practices related to NCD risk. The planned co-creation process will determine which interventions will be most locally relevant, feasible, and needed. The effort aims to empower community members and community health volunteers to drive change that improves their own health and wellbeing. The learnings can be useful nationally and sub-nationally in Malaysia, as well as across similar settings that are working with community stakeholders to reduce noncommunicable disease risk. Trial registration National Medical Research Register, Malaysia; NMRR-20-1004-54787 (IIR); July 7, 2020

Parents, Products, and the Development of Preferences: Child Palate and Food Choice in an Obesogenic Environment

Food systems and the ways food products are formulated, packaged, and marketed contribute to obesogenic environments. The current research focuses on products informally referred to as junk food (foods high in sugar, fat, and salt) and how they function as a mechanism in developing taste preferences in children three to five years old. Across two studies, the authors examine how parents’ taste preferences, their lay theories of self-control, and their resulting decisions about foods to provide to their children are associated with their children’s taste preferences and consumption of healthy food. Using a parent survey, Study 1 examines how parent preferences and exposure to junk food contribute to the development of child food preferences. Study 2, which is based on a parent survey and observation of child meals out of home, confirms Study 1 findings. Furthermore, Study 2 shows how parental lay theories and parental decisions regarding junk food provided to a child are related to the child’s consumption of vegetables. Implications for food brands, policy, and parents are discussed.

Oxidative Stress and Neuroinflammation in a Rat Model of Co-Morbid Obesity and Psychogenic Stress

BackgroundThere is growing recognition for a reciprocal, bidirectional link between anxiety disorders and obesity. Although the mechanisms linking obesity and anxiety remain speculative, this bidirectionality suggests shared pathophysiological processes. Neuroinflammation and oxidative damage are implicated in both pathological anxiety and obesity. This study investigates the relative contribution of comorbid diet-induced obesity and stress-induced anxiety to neuroinflammation and oxidative stress.MethodsThirty-six (36) male Lewis rats were divided into four groups based on diet type and stress exposure: 1) control diet unexposed (CDU) and 2) exposed (CDE), 3) Western-like high-saturated fat diet unexposed (WDU) and 4) exposed (WDE). Neurobehavioral tests were performed to assess anxiety-like behaviors. The catalytic concentrations of glutathione peroxidase and reductase were measured from plasma samples, and neuroinflammatory/oxidative stress biomarkers were measured from brain samples using Western blot. Correlations between behavioral phenotypes and biomarkers were assessed with Pearson’s correlation procedures.ResultsWe found that WDE rats exhibited markedly increased levels of glial fibrillary acidic protein (185%), catalase protein (215%), and glutathione reductase (GSR) enzymatic activity (418%) relative to CDU rats. Interestingly, the brain protein levels of glutathione peroxidase (GPx) and catalase were positively associated with body weight and behavioral indices of anxiety.ConclusionsTogether, our results support a role for neuroinflammation and oxidative stress in heightened emotional reactivity to obesogenic environments and psychogenic stress. Uncovering adaptive responses to obesogenic environments characterized by high access to high-saturated fat/high-sugar diets and toxic stress has the potential to strongly impact how we treat psychiatric disorders in at-risk populations.HighlightsPredatory odor stress heightens footshock reactivity and anxiety-like behaviors in Lewis rats.WD intake increases glutathione reductase activity in plasma.WD intake and PS exposure acted synergistically to increase the brain protein levels of catalase and the glial fibrillary acidic protein.The protein levels and activities of some redox/neuroinflammatory biomarkers are closely associated with behavioral proxies related to fear and anxiety in rats.

‘I’d say I’m fat, I’m not obese’: obesity normalisation in urban-poor South Africa

Objective:In the past decade, South Africa’s obesity epidemic has increased in both children and adults, and being overweight is becoming the norm. Several contributing factors lead to the normalisation of obesity. One of these is the culturally entrenched likeness of larger body sizes or shapes within a milieu of easily accessible unhealthy food and beverages. This qualitative study advances knowledge about the influence of socio-cultural norms and obesogenic environments on weight under estimation and ‘obesity normalisation’ amongst black South Africans living in an urban setting.Design:A theory-based qualitative study used focus group discussions (FGDs) with a semi-structured interview guide. FGDs were transcribed verbatim and analysed thematically using a constant comparison method.Setting:Soweto, Johannesburg, South Africa, is a setting which has undergone rapid urbanisation and nutrition transition with ubiquitous availability of processed and fast-foods.Participants:Adults older than 18 years living in Soweto (n 57).Results:There is a wide misperception about obesity amongst black Africans living in an urban setting in Soweto. Participants who admitted to being fat or overweight did not view themselves as such. This could be attributed to unchanging socio-cultural factors that reinforce the acceptability of bigger bodies and living in obesogenic environment.Conclusions:Without addressing socio-cultural norms that attribute bigger bodies to beauty and wealth, motivating individuals to address weight gain will prove difficult especially for populations living in obesogenic environments. A multi-faceted strategy is required to address obesity in urban South African settings.

Targeting soluble tumor necrosis factor as a potential intervention to lower risk for late-onset Alzheimer’s disease associated with obesity, metabolic syndrome, and type 2 diabetes

Background Insulin impairment and inflammation are two features common to type 2 diabetes and Alzheimer’s disease; however, the molecular and signaling interactions underlying this relationship are not well understood. Mounting evidence point to the associations between the disruption of metabolite processing in insulin impairment and neurodegenerative conditions such as Alzheimer’s. Although the brain depends partially on metabolites processed in the periphery, to date, little is known about how soluble tumor necrosis factor signaling (solTNF) impacts integrated peripheral immune and metabolic feedback signals in states of energy overload and insulin insensitivity. Methods C57Bl/6J mice were fed a high-fat high-carbohydrate diet (HFHC) for 14 weeks. The brain-permeant biologic XPro1595® was used to block solTNF-dependent pathways. Metabolic and immune alterations were evaluated in the gut, liver, and brain. Behavioral tests were performed. Untargeted metabolomics was carried out in the plasma and liver. Results HFHC diet promotes central insulin impairment and dysregulation of immune-modulatory gene expressed in the brain. Alteration of metabolites associated with type 2 diabetes and Alzheimer’s such as butanoate, glutamate, biopterin, branched-chain amino acids, purines, and proteoglycan metabolism was observed in HFHC-fed mice. solTNF inhibition ameliorates hepatic metabolic disturbances and hepatic and intestinal lipocalin-2 levels, and decreases insulin impairment in the brain and behavioral deficits associated with HFHC diet. Conclusions Our novel findings suggest that HFHC diet impacts central insulin signaling and immune-metabolic interactions in a solTNF-dependent manner to increase the risk for neurodegenerative conditions. Our novel findings indicate that selective solTNF neutralization can ameliorate peripheral and central diet-induced insulin impairment and identify lipocalin-2 as a potential target for therapeutic intervention to target inflammation and insulin disturbances in obesogenic environments. Collectively, our findings identify solTNF as a potential target for therapeutic intervention in inflammatory states and insulin disturbances in obesogenic environments to lower risk for AD.