Background/Objectives: People with metabolically healthy obesity (MHO) may still have an increased risk for cardiovascular mortality compared to metabolically healthy lean (MHL) individuals. However, the mechanisms linking obesity to cardiovascular diseases are not entirely understood. We therefore tested the hypothesis that circulating cell adhesion molecules (CAMs) are higher in MHO compared to MHL individuals. Subjects/Methods: Serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin and P-selectin were measured in age- and sex-matched groups of MHL (n = 32), MHO categorized into BMI-matched insulin sensitive (IS, n = 32) or insulin resistant (IR) obesity (n = 32) and people with metabolically unhealthy obesity (MUO, n = 32). Results: Indeed, individuals with MHO have significantly higher sICAM-1, E-selectin, and P-selectin serum concentrations compared to MHL people. However, these CAMs are still significantly lower in IS compared to IR MHO. There was no difference between the groups in sVCAM-1 serum concentrations. Compared to all other groups, circulating adhesion molecules were significantly higher in individuals with MUO. Conclusions: These findings suggest that obesity-related increased cardiovascular risk is reflected and may be mediated by significantly higher CAMs. The mechanisms causing elevated adhesion molecules even in the absence of overt cardio-metabolic risk factors and whether circulating CAMs could predict cardiovascular events need to be explored.

Background: Added flavors are a marker for ultra-processing of food and a strong link exists between the intake of ultra-processed food and the development of obesity. The objective of the present article is to assess animal and human data elucidating the impact of added flavors on the regulation of food intake and body weight gain, as well as to define areas for future research. Main text: Mechanistic studies suggest that added flavors induce overeating and body weight gain by two independent mechanisms: Added flavors promote hedonic eating and override homeostatic control of food intake, as well as disrupt flavor-nutrient learning and impair the ability to predict nutrients in food items. Supporting these potential mechanisms, added flavors increase feed intake and body weight as compared to non-flavored control diets in a broad range of animal studies. They are actively promoted by feed additive manufacturers as useful tools to improve palatability, feed intake, and performance parameters. In humans, added flavors are extensively tested concerning toxicity; however, no data exist concerning their impact on food intake and body weight. Conclusions: Added flavors are potential contributors to the obesity epidemic and further studies focusing on their role in humans are urgently required. These studies include obesity interventions specifically targeting food items with added flavors and cohort studies on independent associations between added flavor intake and metabolic, as well as cardiovascular, morbidity, and mortality.

Obesity has recently been linked with reduced fertility, and the mechanisms underpinning this effect are currently unknown. The adipokine leptin is dysregulated in obesity and affects reproductive tracts; therefore, we investigated the dose-dependent effects of leptin on Leydig cell function and spermatogenesis. Eight-week-old leptin-deficient obese (ob/ob) male mice were treated with subphysiological (0.1- or 0.5-mg/kg body weight [BW]/d) or physiological (3.0-mg/kg BW/d) doses of leptin or saline for 12 weeks (chronic treatment) or 72 hours (acute treatment). We then evaluated male reproductive function markers. Mean testis weight increased significantly in the 0.1- and 3.0-mg/kg BW/d groups compared with saline controls (both P < .05). Intratesticular testosterone levels relative to testis weight significantly increased in the 0.5-mg/kg BW/d group compared with saline controls (P < .05). FSH levels increased in a dose-dependent manner with leptin treatment, whereas LH levels did not change. Leptin treatment significantly up-regulated both mRNA and protein expression of the steroidogenic enzyme cytochrome P450 17A1. Spermatogenesis improved in leptin-treated animals. Significantly more seminiferous tubules were observed in stages I–VIII (P < .01), and there were fewer abnormal seminiferous tubule structures (P < .01). Acute treatment with physiological leptin doses partially improved male reproductive markers without changing BW. Administration of subphysiological to physiological doses of leptin improves Leydig cell function and spermatogenesis.

Tissue inhibitor of metalloproteinase (TIMP)‐1 is an adipocyte‐secreted protein upregulated in obesity which promotes adipose tissue development. Furthermore, the proinflammatory adipocytokines tumor necrosis factor α (TNFα) and interleukin (IL)‐6 induce insulin resistance, and plasma concentrations are increased during weight gain. In the current study, the impact of TNFα and IL‐6 on TIMP‐1 mRNA and protein expression was determined in 3T3‐L1 adipocytes. Interestingly, TNFα and IL‐6 induced TIMP‐1 protein secretion more than 3‐ and 2‐fold, respectively. Furthermore, TIMP‐1 mRNA was upregulated in a time‐ and dose‐dependent fashion. Inhibitor experiments suggested that nuclear factor κB and p44/42 mitogen‐activated protein kinase are involved in both, basal and adipocytokine‐induced TIMP‐1 expression. Moreover, the thiazolidinedione troglitazone partly reversed TNFα‐ but not IL‐6‐induced TIMP‐1 synthesis. Taken together, we demonstrate that TIMP‐1 expression is selectively upregulated in fat cells by proinflammatory adipocytokines and might play a role in maintaining adipose tissue mass in obesity.

The prevalence of dementia is increasing globally and is linked to obesity and unfavorable dietary habits. The present study analyses the association of alcohol intake from wine and non-wine alcoholic beverages (non-wine) in g/d, as well as coffee and tea in cups/d, with incident dementia. Over 4.2 million person-years, 4270 dementia cases occurred in 351,436 UK Biobank participants. Hazard ratios (HRs) for incident dementia were defined with Cox proportional hazard regression models in which beverage intake was fitted as penalized cubic splines. Wine intake showed a significant U-shaped association with the lowest risk for incident dementia (nadir) ranging from 21 to 23 g alcohol/d in all participants and in males. In contrast, non-wine consumption was significantly and dose-dependently associated with incident dementia, and the nadir was found at 0 g alcohol/d. Coffee consumption was not related to dementia risk, while moderate-to-high tea intake was negatively associated with incident dementia. Taken together, the current study shows on a population level that moderate consumption of wine and moderate-to-high tea intake is associated with a decreased risk of incident dementia. In contrast, non-wine is positively related to dementia risk in a linear fashion, and no clear association is found for coffee.

The present study examines how alcohol intake from wine and non-wine alcoholic beverages (non-wine) in g/d, as well as cups of coffee and tea included as continuous covariates and mutually adjusted are associated with all-cause, cancer, non-cancer and CVD mortality. Consumption was assessed in 354 386 participants of the UK Biobank cohort who drank alcohol at least occasionally and survived at least 2 years after baseline with 20 201 deaths occurring over 4·2 million person-years. Hazard ratios (HR) for mortality were assessed with Cox proportional hazard regression models and beverage intake fitted as penalised cubic splines. A significant U-shaped association was detected between wine consumption and all-cause, non-cancer and CVD mortality. Wine consumption with lowest risk of death (nadir) ranged from 19 to 23 g alcohol/d in all participants and both sexes separately. In contrast, non-wine intake was significantly and positively associated in a dose-dependent manner with all mortality types studied except for CVD in females and with the nadir between 0 and 12 g alcohol/d. In all participants, the nadir for all-cause mortality was 2 cups coffee/d with non-coffee drinkers showing a slightly increased risk of death. Tea consumption was significantly and negatively associated with all mortality types in both sexes. Taken together, light to moderate consumption of wine but not non-wine is associated with decreased all-cause and non-cancer mortality. A minor negative association of coffee consumption with mortality cannot be excluded whereas tea intake is associated with a consistently decreased risk of all mortality types studied.