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The written thesis describes thermogenic adipocytes in the inguinal adipose tissue of infant mice. A mitochondria to nucleus signaling was discovered which supports beige adipogenesis. The understanding of infant adipose tissue development allowed new insights into the adipose tissue field to target obesity development in adults.

In current study, we demonstrated a special and distinct modulation pattern of monocytes in sepsis patients with different metabolic disturbance. As a novel finding, we identified the selective diminution of CD14+ (Classical monocytes) and CD33 expression in monocytes in sepsis. This effect is more pronounced in patients with diabetes during progression of sepsis and septic shock. Obese diabetic patients have higher non-classical monocyte counts in non-sepsis and increase CD16 expression as well as CD163 under septic conditions.

Obesity is a pandemic medical condition, which causes a set of comorbidities, including cardiovascular diseases, hypertension, dyslipidemia, insulin resistance and type II diabetes mellitus. Also, there is a prevalence of childhood obesity all around the world today. To understand the onset and to prevent childhood obesity seems to be a crucial task in the 21st century. In this dissertation, I have studied adipose tissue development during infancy, with focus on the interaction between adipose cells and so-called tissue macrophages (ATMs). Understanding this interaction might be critical for maintaining a healthy adipose tissue environment and can help to prevent the onset of obesity. I have studied the role of an appetite-regulating neurohormone, so-called neuropeptide FF (NPFF) in the early development of the adipose tissue and found that NPFF can help to sustain a healthy adipose tissue microenvironment by affecting both adipocytes and ATMs. In this thesis I also show that an ether lipid family, so-called alkylglycerols (AKGs) are enriched in breast milk and are necessary for adipose tissue development in infancy. AKGs can be metabolized by ATMs into platelet activating factor (PAF), and PAF can induce interleukin-6 (IL-6) production and activate the IL-6/STAT3 signaling pathway in adipocytes, which triggers a fat-oxidizing and heat-generating adipose tissue development. The AKG-controlled communication between ATMs and adipocytes however potentially can lead to inflammation, and NPFF is necessary to avoid such unfavorable effect of AKGs by promoting their catabolism. NPFF is hence important for adipose tissue quality, and the healthy transformation of the fat-oxidizing infant adipose tissue into a fat-storing, adult adipose tissue.

The regulation of macrophage homeostasis is relevant in health and in the development of diseases. As metabolically relevant immune cells of the adipose tissue (AT), adipose tissue macrophages (ATMs) contribute to AT inflammation, which is dependant on the number and the activation state of ATMs. Herein, ATM homeostasis of white AT depots from lean adult mice was shown to be maintained by yolk sac-derived macrophages through their ability to undergo cell division to self-renew. However, blood monocytes also contributed to the maintenance of ATM homeostasis after bone marrow transplantation. Furthermore, ATM self-renewal was shown to be influenced by endocrine signals. The endocrine disruptor bisphenol A (BPA), which preferably bioaccumulates in the AT, increased macrophage self-renewal and mildly affected their activation states, without affecting their function in vitro. This increase in self-renewal was associated with increased phosphorylation of extracellular signal-regulated kinase and a slight increase in liver X receptor alpha (LXRα) expression, whose inhibition induced, whereas its activation impeded macrophage self-renewal. In addition, self-renewing (Ki67+) macrophages expressed lower LXRα levels than quiescent (Ki67-) macrophages. Correspondingly, tissue-resident macrophage pools with increased Ki67- macrophages had elevated LXRα expression levels and Ki67+ macrophages decreased LXRα expression. Moreover, LXR signaling modulated the self-renewal of classically activated (M1) and alternatively activated (M2) macrophages by either reducing or increasing the number of macrophages in vitro, respectively. Over all, these data show that BPA unconsciously released into the environment can impede ATM homeostais, whereas LXRα signaling may protect from uncontrolled macrophage expansion, which is associated with the onset of obesity and its associated metabolic syndrome.