ABSTRACT
Syndemics theory has been applied to the structurally shaped, biologically facilitated co-occurrence of HIV/AIDS with Neglected Tropical Diseases (NTDs) and with sexually transmitted infections (STIs). The biological and social pathways of interaction between all three ailments have not yet been analysed together. The effects of these diseases are often exacerbated by structural factors including access to care and socioeconomic status. We explore the interrelated biological pathways and structural factors that have further heightened the risk for HIV/AIDS, NTDs, and STIs. Furthermore, we argue women in rural areas are at an increased risk for all three diseases due to biological and social factors including increased distance to quality care and lower reproductive autonomy. This paper integrates the established syndemics of HIV/NTDs and HIV/STIs within the historical and modern contexts of colonisation and neo-colonisation in Nigeria. We explore the effects of colonisation on women's health by evaluating the influence of foreign aid policies, structural programmes, and shifting gender norms. Applying a syndemic approach, juxtaposed by historical contextualisation, offers important implications for the prevention and treatment of HIV/AIDS, STIs, and NTDs. Our analysis suggests a perspective through which to view health of regions with a history of colonisation.
Subject(s)
Eugenics , HIV Infections/epidemiology , International Cooperation , Neglected Diseases/epidemiology , Sexually Transmitted Diseases/epidemiology , Syndemic , Women's Health , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/prevention & control , Adult , Female , HIV Infections/prevention & control , Health Services Accessibility , Humans , Neglected Diseases/prevention & control , Nigeria/epidemiology , Prevalence , Reproductive Health , Rural Population , Sexually Transmitted Diseases/prevention & controlABSTRACT
CDP138 is a calcium- and lipid-binding protein that is involved in membrane trafficking. Here, we report that mice without CDP138 develop obesity under normal chow diet (NCD) or high-fat diet (HFD) conditions. CDP138-/- mice have lower energy expenditure, oxygen consumption, and body temperature than wild-type (WT) mice. CDP138 is exclusively expressed in adrenal medulla and is colocalized with tyrosine hydroxylase (TH), a marker of sympathetic nervous terminals, in the inguinal fat. Compared with WT controls, CDP138-/- mice had altered catecholamine levels in circulation, adrenal gland, and inguinal fat. Adrenergic signaling on cyclic AMP (cAMP) formation and hormone-sensitive lipase (HSL) phosphorylation induced by cold challenge but not by an exogenous ß3 adrenoceptor against CL316243 were decreased in adipose tissues of CDP138-/- mice. Cold-induced beige fat browning, fatty acid oxidation, thermogenesis, and related gene expression were reduced in CDP138-/- mice. CDP138-/- mice are also prone to HFD-induced insulin resistance, as assessed by Akt phosphorylation and glucose transport in skeletal muscles. Our data indicate that CDP138 is a regulator of stress response and plays a significant role in adipose tissue browning, energy balance, and insulin sensitivity through regulating catecholamine secretion from the sympathetic nervous terminals and adrenal gland.
Subject(s)
Adipose Tissue, Brown/metabolism , Catecholamines/metabolism , Homeodomain Proteins/metabolism , Insulin Resistance/physiology , Membrane Proteins/metabolism , Protein Transport/physiology , Adrenal Glands/metabolism , Animals , Cell Membrane/metabolism , Diet, High-Fat/adverse effects , Energy Metabolism/physiology , Gene Expression/physiology , Lipid Metabolism/physiology , Mice , Mice, Inbred C57BL , Muscle, Skeletal/metabolism , Phosphorylation/physiology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/physiology , Sterol Esterase/metabolism , Thermogenesis/physiologyABSTRACT
Inflammation plays a significant role in the development of obesity-related complications, but the molecular events that initiate and propagate such inflammation remain unclear. Here, we report that mice fed a high-fat diet (HFD) for as little as 1-3 days show increased differentiation of myeloid progenitors into neutrophils and monocytes but reduced B lymphocyte production in the bone marrow. Levels of neutrophil elastase (NE) and the nuclear factors CCAAT/enhancer-binding protein α (C/EBPα) and growth factor-independent 1 (GFI-1) are elevated in hematopoietic stem and progenitor cells from HFD-fed mice, but mice lacking either NE or C/EBPα are resistant to HFD-induced myelopoiesis. NE deletion increases expression of the inhibitory isoform of p30 C/EBPα, impairs the transcriptional activity of p42 C/EBPα, and reduces expression of the C/EBPα target gene GFI-1 in hematopoietic stem and progenitor cells, suggesting a mechanism by which NE regulates myelopoiesis. Furthermore, NE deletion prevents HFD-induced vascular leakage. Thus, HFD feeding rapidly activates bone marrow myelopoiesis through the NE-dependent C/EBPα-GFI-1 pathway preceding vascular damage and systemic inflammation.
