Nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with obesity and insulin resistance, is characterized by hepatic lipid accumulation and activation of the endoplasmic reticulum (ER) stress response. The sirtuin 2 (SIRT2) protein deacetylase is emerging as a new player in metabolic homeostasis, but its role in the development of hepatic steatosis and its link with ER stress activation remains unknown. SIRT2-knockout (SIRT2-KO) and wild-type mice were fed either a control or a high-fat diet (HFD) for 4 weeks. Genetic manipulation of SIRT2 levels was performed in human hepatic cells. Although apparently normal under a control diet, SIRT2-KO mice showed accelerated body weight gain and adiposity on a HFD, accompanied by severe insulin resistance. Importantly, SIRT2-KO mice exhibited worsened hepatic steatosis independently from diet, consistent with upregulated gene expression of lipogenic enzymes and increased expression of ER stress markers. Exposure of hepatic cells to palmitate induced lipid accumulation, increased ER stress, and decreased SIRT2 expression. Moreover, SIRT2-silenced cells showed enhanced lipid accumulation and ER stress activation under basal conditions, whereas SIRT2 overexpression abrogated palmitate-induced lipid deposition and ER stress activation. Our findings reveal a role for SIRT2 in the regulation of hepatic lipid homeostasis, potentially through the ER stress response, suggesting that SIRT2 activation might constitute a therapeutic strategy against obesity and its metabolic complications.

Background Non-communicable diseases are a leading cause of health loss worldwide, in part due to unhealthy lifestyles. Metabolic-based diseases are rising with an unhealthy body-mass index (BMI) in rural areas as the main risk factor in adults, which may be amplified by wider determinants of health. Changes in rural environments reflect the need of better understanding the factors affecting the self-ability for making balanced decisions. We assessed whether unhealthy lifestyles and environment in rural neighbourhoods are reflected into metabolic risks and health capability. Methods We conducted a community-based cross-sectional study in 15 Portuguese rural neighbourhoods to describe individuals’ health functioning condition and to characterize the community environment. We followed a qualitatively driven mixed-method design to gather information about evidence-based data, lifestyles and neighbourhood satisfaction (incorporated in eVida technology), within a random sample of 270 individuals, and in-depth interviews to 107 individuals, to uncover whether environment influence the ability for improving or pursuing heath and well-being. Results Men showed to have a 75% higher probability of being overweight than women (p-value = 0.0954); and the reporting of health loss risks was higher in women (RR: 1.48; p-value = 0.122), individuals with larger waist circumference (RR: 2.21; IC: 1.19; 4.27), overweight and obesity (RR: 1.38; p-value = 0.293) and aged over 75 years (RR: 1.78; p-value = 0.235; when compared with participants under 40 years old). Metabolic risks were more associated to BMI and physical activity than diet (or sleeping habits). Overall, metabolic risk linked to BMI was higher in small villages than in municipalities. Seven dimensions, economic development, built (and natural) environment, social network, health care, demography, active lifestyles, and mobility, reflected the self-perceptions in place affecting the individual ability to make healthy choices. Qualitative data exposed asymmetries in surrounding environments among neighbourhoods and uncovered the natural environment and natural resources specifies as the main value of rural well-being. Conclusions Metabolic risk factors reflect unhealthy lifestyles and can be associated with environment contextual-dependent circumstances. People-centred approaches highlight wider socioeconomic and (natural) environmental determinants reflecting health needs, health expectations and health capability. Our community-based program and cross-disciplinary research provides insights that may improve health-promoting changes in rural neighbourhoods.

Amyotrophic lateral sclerosis (ALS) is a serious disease of the nervous system, in which the brain and spinal cord cannot communicate properly with the muscles to coordinate the body’s movements. Consequently, the muscles gradually stop working and things like walking, eating, breathing, and speaking become more and more difficult. Many aspects of ALS remain a mystery, but we know that cells called neurons run out of energy in ALS patients, resulting in the loss of communication with muscles. This happens due to defects in mitochondria—the tiny structures within our cells that produce energy. Researchers have been working hard to discover how to keep mitochondria healthy, avoid the death of nerve cells, and ultimately restore the communication between neurons and muscles.

Background: Non-communicable diseases (NCDs) are a leading cause of health loss worldwide, in part due to unhealthy lifestyles. Metabolic-based diseases are rising with an unhealthy body-mass index (BMI) in rural areas as the main risk factor in adults. Health loss risks in rural areas may be amplified by wider determinants such as socio-demography and surrounding environments. We assessed weather (un)healthy lifestyles and environment in rural neighbourhoods are reflected into metabolic risks and health capability, and how community circumstances may impact the self-ability for making balanced decisions.Methods: We conducted a community-based cross-sectional study in fifteen Portuguese rural neighbourhoods (with high ageing index and high illiteracy) to describe individuals’ health functioning condition and to characterize the community environment. We followed a qualitatively driven mixed-method design, using a healthy lifestyle assessment toolkit, to gather evidence-based data and lifestyles (incorporated in eVida technology), within a random sample of 270 individuals; and 107 in-depth interviews to determine whether environment influence the capability for improving or pursuing heath and well-being.Results: Men showed to have a 75% higher probability of being overweight than women (p-value=0.0954); and the reporting of health loss risks was higher in women (RR: 1.48; p-value=0.122), individuals with larger waist circumference (RR: 2.21; IC: 1.19; 4.27), overweight and obesity (RR: 1.38; p-value=0.293) and participants aged over 75 years (RR: 1.78; p-value= 0.235; when compared with participants under 40 years old). Metabolic risks were more associated to BMI and physical activity than diet (or sleeping habits); participants strongly evidenced the adherence to a Mediterranean dietary pattern. From the interviews, we identified seven environmental circumstances reflecting health needs, health expectations and health capability: economic development, built environment, social network, health care, demography, active lifestyles, and mobility. And, while the starting point of the interview addressed community needs, participants expressed the value of natural environment in their neighbourhood as the main positive effect to pursuing health and well-being, with particular emphasis to lower exposure to air / noise pollution, daily routines linked to nature or land use, and diversity of nature experiences.Conclusions: Our qualitatively driven mixed-method design, involving the community, uncovers environment contextual-dependent circumstances influencing the ability of individuals to pursue healthy habits. The active participation of local representatives, with its degrees of negotiation and flexibility, contributed to adapt the health-related messages. The co-benefits from this co-designing community program advance the evidence to support academy-community driven interventions for pushing health and well-being at a broader social, health care and (natural) environment agenda in rural neighbourhoods.