Building research in diet and cognition (BRIDGE): Baseline characteristics of older obese African American adults in a randomized controlled trial to examine the effect of the Mediterranean diet with and without weight loss on cognitive functioning.

In the United States, >5.4 million people age 65 and older are affected by cognitive impairment and dementia, including Alzheimer's disease. African Americans are more likely than non-Hispanic whites to suffer from these disorders. Obesity is linked to accelerated age-related cognitive decline, and weight loss through caloric restriction is a potential strategy to prevent this cognitive impairment. Adherence to a healthful dietary pattern, such as the Mediterranean Diet (MedDiet), has also shown positive effects on reducing risk for dementia. African Americans are disproportionately affected by obesity and have less healthful diets than non-Hispanic whites. We present baseline characteristics from a three-arm randomized controlled trial that randomized 185 obese (BMI ≥ 30 kg/m2 and ≤ 50 kg/m2) healthy older adults (55-85 years of age) to: 1) Typical Diet Control (TDC); 2) MedDiet alone (MedDiet-A) intervention; or 3) MedDiet caloric restricted intervention to promote weight loss (MedDiet-WL). The majority of the sample was African American (91.4%) and female (85.9%). The two active interventions (MedDiet-A and MedDiet-WL) met once weekly for 8 months, and the TDC received weekly general health newsletters. Baseline data were collected between January 2017 and July 2019 in Chicago, IL. In our sample, closer adherence to a MedDiet pattern was associated with higher attention and information processing (AIP) and higher executive functioning (EF). Consistent with the literature, we saw that older participants performed more poorly on the cognitive assessments than younger participants, and women outperformed men across verbally mediated tasks, especially ones related to learning and memory.

The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity.

Obesity-induced inflammation originating from expanding adipose tissue interferes with insulin sensitivity. Important metabolic effects have been recently attributed to IL-1ß and IL-18, two members of the IL-1 family of cytokines. Processing of IL-1ß and IL-18 requires cleavage by caspase-1, a cysteine protease regulated by a protein complex called the inflammasome. We demonstrate that the inflammasome/caspase-1 governs adipocyte differentiation and insulin sensitivity. Caspase-1 is upregulated during adipocyte differentiation and directs adipocytes toward a more insulin-resistant phenotype. Treatment of differentiating adipocytes with recombinant IL-1ß and IL-18, or blocking their effects by inhibitors, reveals that the effects of caspase-1 on adipocyte differentiation are largely conveyed by IL-1ß. Caspase-1 and IL-1ß activity in adipose tissue is increased both in diet-induced and genetically induced obese animal models. Conversely, mice deficient in caspase-1 are more insulin sensitive as compared to wild-type animals. In addition, differentiation of preadipocytes isolated from caspase-1(-/-) or NLRP3(-/-) mice resulted in more metabolically active fat cells. In vivo, treatment of obese mice with a caspase-1 inhibitor significantly increases their insulin sensitivity. Indirect calorimetry analysis revealed higher fat oxidation rates in caspase-1(-/-) animals. In conclusion, the inflammasome is an important regulator of adipocyte function and insulin sensitivity, and caspase-1 inhibition may represent a novel therapeutic target in clinical conditions associated with obesity and insulin resistance.

Differential susceptibility to lethal endotoxaemia in mice deficient in IL-1α, IL-1ß or IL-1 receptor type I.

The role of intereukin-1 (IL-1) in mortality caused by endotoxaemia remains controversial. While IL-1 receptor antagonist (IL-1Ra) protects mice from lethal endotoxaemia, mice deficient in IL-1ß (IL-1ß⁻( /)⁻) display normal susceptibility to lipopolysaccharide (LPS). The aim of this study was to identify the source of these discrepancies. Mice deficient in IL-1α, IL-1ß or IL-1R type I were injected intraperitoneally with Escherichia coli or Salmonella typhimurium LPS. Survival of the mice was examined and compared with C57/Bl6 wild-type mice. In addition, serum cytokine concentrations were determined after LPS challenge and in vitro cytokine production by peritoneal macrophages was analysed. Clearance of radioactive IL-1α was examined in IL-1α⁻(/)⁻ and wild-type mice. IL-1ß⁻(/)⁻ mice were normally susceptible to endotoxaemia and cytokine production did not differ from that in control mice. Surprisingly, LPS mortality in IL-1α⁻(/)⁻ mice was significantly greater than that in control mice, accompanied by higher interferon-γ release. These effects were mediated by a distorted homeostasis of IL-1RI receptors, as shown by a strongly delayed clearance of IL-1α. In contrast to the IL-1α⁻(/)⁻ and IL-1ß⁻(/)⁻ mice, IL-1RI⁻(/)⁻ mice were completely resistant to high doses of LPS. In conclusion, IL-1RI-mediated signals are crucial in mediating mortality occurring as a result of lethal endotoxaemia. Investigation of IL-1-mediated pathways in IL-1 knock-out mice is complicated by a distorted homeostasis of IL-1Rs.