DACRA induces profound weight loss, satiety control, and increased mitochondrial respiratory capacity in adipose tissue.

BACKGROUND AND OBJECTIVES: Dual amylin and calcitonin receptor agonists (DACRAs) are therapeutic candidates in the treatment of obesity with beneficial effects on weight loss superior to suppression of food intake. Hence, suggesting effects on energy expenditure by possibly targeting mitochondria in metabolically active tissue. METHODS: Male rats with HFD-induced obesity received a DACRA, KBP-336, every third day for 8 weeks. Upon study end, mitochondrial respiratory capacity (MRC), - enzyme activity, - transcriptional factors, and -content were measured in perirenal (pAT) and inguinal adipose tissue. A pair-fed group was included to examine food intake-independent effects of KBP-336. RESULTS: A vehicle-corrected weight loss (23.4 ± 2.8%) was achieved with KBP-336, which was not observed to the same extent with the food-restricted weight loss (12.4 ± 2.8%) (P < 0.001). Maximal coupled respiration supported by carbohydrate and lipid-linked substrates was increased after KBP-336 treatment independent of food intake in pAT (P < 0.01). Moreover, oligomycin-induced leak respiration and the activity of citrate synthase and ß-hydroxyacetyl-CoA-dehydrogenase were increased with KBP-336 treatment (P < 0.05). These effects occurred without changes in mitochondrial content in pAT. CONCLUSIONS: These findings demonstrate favorable effects of KBP-336 on MRC in adipose tissue, indicating an increased energy expenditure and capacity to utilize fatty acids. Thus, providing more mechanistic insight into the DACRA-induced weight loss.

Effect of Simvastatin Treatment on Mitochondrial Function and Inflammatory Status of Human White Adipose Tissue.

BACKGROUND: Statin therapy has shown pleiotropic effects affecting both mitochondrial function and inflammatory status. However, few studies have investigated the concurrent effects of statin exposure on mitochondrial function and inflammatory status in human subcutaneous white adipose tissue. OBJECTIVES: In a cross-sectional study, we investigated the effects of simvastatin on mitochondrial function and inflammatory status in subcutaneous white adipose tissue of 55 human participants: 38 patients (19 females/19 males) in primary prevention with simvastatin (> 40 mg/d, > 3 mo) and 17 controls (9 females/8 males) with elevated plasma cholesterol. The 2 groups were matched on age, body mass index, and maximal oxygen consumption. METHODS: Anthropometrics and fasting biochemical characteristics were measured. Mitochondrial respiratory capacity was assessed in white adipose tissue by high-resolution respirometry. Subcutaneous white adipose tissue expression of the inflammatory markers IL-6, chemokine (C-C motif) ligand 2 (CCL2), CCL-5, tumor necrosis factor-α, IL-10, and IL-4 was analyzed by quantitative PCR. RESULTS: Simvastatin-treated patients showed lower plasma cholesterol (P < .0001), low-density lipoprotein (P < .0001), and triglyceride levels (P = .0116) than controls. Simvastatin-treated patients had a lower oxidative phosphorylation capacity of mitochondrial complex II (P = .0001 when normalized to wet weight, P < .0001 when normalized to citrate synthase activity [intrinsic]), and a lower intrinsic mitochondrial electron transport system capacity (P = .0004). Simvastatin-treated patients showed higher IL-6 expression than controls (P = .0202). CONCLUSION: Simvastatin treatment was linked to mitochondrial respiratory capacity in human subcutaneous white adipose tissue, but no clear link was found between statin exposure, respiratory changes, and inflammatory status of adipose tissue.

"How to have healthy children". Responses to the falling birth rate in Norway, c. 1900-1940.

This paper focuses on initiatives to improve infant health, as they developed in Norway especially during the interwar period. Falling birth rates were felt as a menace to the survival of the nation and specific initiatives were taken to oppose it. But crises engendered by the reduction in fertility strengthened opportunities for introducing policies to help the fewer children born survive and grow up to become healthy citizens. Legislation supporting mothers started in 1892 increased in the interwar years including economic features. Healthy mother and baby stations and hygienic clinics, aimed at controlling births were developed by voluntary organisations inspired from France and England respectively. A sterilization law (1934) paralleled some German policies.

IL-20 is an arteriogenic cytokine that remodels collateral networks and improves functions of ischemic hind limbs.

Successful therapeutic angiogenesis for the treatment of ischemic disorders relies on selection of optimal proangiogenic or arteriogenic agents that are able to promote establishment of functional collateral networks. Here, we show that IL-20, a pleiotropic inflammatory cytokine, displays an imperative effect on vascular remodeling. Stimulation of both large and microvascular endothelial cells with IL-20 leads to activation of receptor-dependent multiple intracellular signaling components, including increased phosphorylation levels of JAK2/STAT5, Erk1/2, and Akt; activation of small GTP-binding proteins Rac and Rho; and intracellular release of calcium. Surprisingly, IL-20 significantly promotes endothelial cell tube formation without affecting their proliferation and motility. These findings suggest that the vascular function of IL-20 involves endothelial cell organization, vessel maturation, and remodeling. Consistent with this notion, delivery of IL-20 to the ischemic muscle tissue significantly improves arteriogenesis and blood perfusion in a rat hind-limb model. Our findings provide mechanistic insights on vascular functions of IL-20 and define therapeutic implication of this cytokine for the treatment of ischemic disorders.

[Information campaigns in the fight against tuberculosis until about 1940]. / Opplysningskampanjer i kampen mot tuberkulose frem til ca. 1940.

BACKGROUND: Already before the advent of vaccination and antibiotics in Norway in the 1940s, mortality from tuberculosis was heavily reduced. Initiatives from central and local authorities, the efforts of housewives in the homes and the activity of voluntary organizations were attempts to obtain this result. This article focuses on information campaigns staged by the National Association Against Tuberculosis between 1910 and 1920. MATERIAL: Annual reports from the National Association, the Association's journal, the archive from the Lyster Sanatorium in the Bergen Town Archives, and earlier literature on this theme. RESULTS: The Association Against Tuberculosis organised extensive information campaigns through lectures, leaflets, its journal, and "travelling teachers", targeting the general public as well as defined groups. Men were especially admonished to stop spitting, women to keep the home clean, and patients to follow doctor's instructions. INTERPRETATION: The information campaigns were part of comprehensive efforts made by voluntary organizations, public authorities, doctors and housewives to reduce the mortality of tuberculosis before the advent of vaccination. Higher standards of living also contributed to goal attainment.