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Amyloid-β (Aβ) peptide, which is generated from proteolytic cleavage of amyloid precursor protein (APP), is a key molecule involved in the pathology of Alzheimer disease. Both APP and Aβ peptides are expressed in adipose tissue, however it is currently unclear whether Aβ can affect the key functions of adipose tissue. We aimed to explore whether Aβ affected lipolysis and adipokine secretion in cultured human adipose tissue. We found that Aβ25–35, which contains the main functional domain of the Aβ, stimulated lipolysis via PKA and ERK1/2-dependent pathways and that Aβ25–35induced leptin and IL-6 secretion. It is concluded that Aβ peptide exerts functional effects on adipose tissue that may lead to increased release of free fatty acids and pro-inflammatory adipokines. [ABSTRACT FROM PUBLISHER]

Adipose tissue secretes numerous hormone-like factors, which are known as adipokines. Adipokine receptors have been identified in the central nervous system but the potential role of adipokine signaling in neuroprotection is unclear. The aim of this study is to determine (1) Whether adipokines secreted from cultured adipose tissue of lean humans is protective against oxidative stress-induced neurotoxicity in human SH-SY5Y neuronal cells; and (2) To explore potential signaling pathways involved in these processes. Adipose tissue conditioned media (ATCM) from healthy lean subjects completely prevented H2O2 induced neurotoxicity, while this effect is lost after heating ATCM. ATCM activated the phosphorylation of ERK1/2, JNK and Akt at serine 308 in SH-SY5Y cells. PD98059 (25 µM), SP600125 (5 µM) and LY29400 (20 µM) partially blocked the protective effects of ATCM against H2O2 induced neurotoxicity. Findings demonstrate that heat-sensitive factors secreted from human adipose tissue of lean subjects are protective against H2O2 induced neurotoxicity and ERK1/2, JNK, and PI3K signaling pathways are involved in these processes. In conclusion, this study demonstrates preliminary but encouraging data to further support that adipose tissue secreted factors from lean human subjects might possess neuroprotective properties and unravel the specific roles of ERK1/2, JNK and PI3K in these processes. [ABSTRACT FROM AUTHOR]

Background Peripheral blood mononuclear cells (PBMCs) are known to respond to systematic changes in nutrient availability. The impact of a short-term high fat diet (HFD), with and without acute glucose ingestion, on the energy-sensing enzyme 5' AMP-activated protein kinase (AMPK) as well as mitochondrial oxidative phosphorylation (OXPHOS) proteins in PBMCs is currently unknown. Methods Nine healthy, lean young males participated in a 7 day HFD intervention, designed to induce transient glucose intolerance. The phosphorylation status and total protein content of AMPK and inflammatory mitogen-activated protein kinases (MAPKs), and total OXPHOS protein in PBMCs, along with circulating cytokines, were assessed in the fasted state and following an oral glucose tolerance test (OGTT) before and after the HFD. Results One week of HFD resulted in relative glucose intolerance. The HFD resulted in a reduction of AMPK phosphorylation under fasting basal conditions and following the OGTT (both P < 0.05), while there were no differences in OXPHOS protein expression. Although the short-term HFD had no effect on basal phosphorylation of p38, JNK or ERK1/2, the activation of MAPKs signalling in response to glucose ingestion was attenuated post-HFD as compared to pre-HFD (P < 0.05 for all). Circulating cytokines were not significantly affected by the HFD. Conclusions We conclude that impaired glucose tolerance in response to 7 day HFD resulted in decreased AMPK activity and impaired glucose-stimulated MAPK activation following glucose ingestion in vivo in PBMCs from young, lean subjects. Further studies are warranted to explore how dietary manipulations impact interplay between AMPK and inflammatory signalling, along with immune function, in PBMCs. [ABSTRACT FROM AUTHOR]