Obesity is one of the most immediate health threats in industrialized countries, increasing morbidity and mortality.  It is characterized by an excessive increase of white adipose tissue. Adipose tissue is a tissue with high plasticity, having the ability to expand throughout the entire lifespan. In obesity, adipocytes become very large and the vasculature of adipose tissue is unable to grow along to provide oxygen to adipocytes, leading to local adipose tissue hypoxia. Hypoxia was reported to occur in adipose tissue in obese mice and humans. Hypoxia has a high impact in adipose tissue homeostasis, contributing to adipose tissue dysfunction in obesity. However, the impact of hypoxia on adipocyte physiology is not fully understood.

Fig. 1. Effects of normoxia (A) and hypoxia mimetic (B) in the physiology of adipocyte. (A) In normoxia conditions, adipocytes differentiate with an increase of PPARγ2 expression and increase of lipid accumulation (B) In hypoxic conditions (mimetic), adipocytes do not express PPARγ2 but with increased lipid accumulation. Hypoxia mimetic also increases miR27a and miR27b expression. Cobalt chloride also induces the production of reactive oxygen species and autophagy and decreases ATP production.

In the paper that we published we evaluated the impact of the oxygen decrease (hypoxia) in adipose tissue by treating adipocytes with hypoxia mimetics, cobalt chloride and deferoxamine. We observed that hypoxia mimetic has several deleterious effects in normal adipocyte function. Hypoxia blocks the differentiation of adipocytes but increases the accumulation of lipids by these cells.

Furthermore, hypoxia mimetic induces mitochondrial dysfunction, lactate and reactive oxygen species production and decreases ATP, decreasing the energy needed for the normal function of the cell. These results together suggest that hypoxia effects on adipocyte function occur through mitochondrial dysfunction and reactive oxygen species production. Hypoxia was also observed to induce autophagy, which is a physiological protective mechanism that is also described to be mediated by reactive oxygen species.

Although further studies are needed for a better understanding of the effect of hypoxia in adipocyte physiology, these results highlight the importance of hypoxia in adipocyte function and provides a possible explanation for hypoxic lipogenesis.

Ana Patrícia Marques ^1,2, Joana Rosmaninho-Salgado ^1,3, Marta Estrada ¹, Vera Cortez ¹,
Rui Jorge Nobre ¹, Cláudia Cavadas ^1,4
1CNC – Center for Neuroscience and Cell Biology, University of Coimbra, Portugal
²PDBEB – Doctoral Program in Experimental Biology and Biomedicine,
Interdisciplinary Research Institute (III-UC), University of Coimbra, Portugal
³Department of Medical Genetics, Pediatric Unit, Coimbra Hospital and Universitary Center (CHUC), Coimbra, Portugal
⁴Faculty of Pharmacy, University of Coimbra, Portugal

Publication

Hypoxia mimetic induces lipid accumulation through mitochondrial dysfunction and stimulates autophagy in murine preadipocyte cell line.
Marques AP, Rosmaninho-Salgado J, Estrada M, Cortez V, Nobre RJ, Cavadas C
Biochim Biophys Acta. 2017 Mar

Read offline:     

Related Articles:

	Naturally occurring peptide may tackle the “root… Obesity typically occurs when a person eats more calories than they need for their daily activity. It results in a build-up of fatty tissue around all organs. In lean people,…
	Lipids keeps shrinking with aging and neurodegeneration I remember when my Biology teacher at the secondary school introduced us for the first time to the biochemical components of the living cells. I was immediately fascinated by the…
	When will my mouse die? The maintenance of health is ensured by the function of the three homeostatic systems of the body: the nervous, endocrine and immune systems, and by the net that allows crosstalk…
	Other components of less common oilseeds are much… Polyunsaturated fatty acids (PUFA) are thought to be some of the most important nutrients and health promoting constituents, the presence of which is usually insufficient in a daily diet, which…
	Historical stability of the human aging rate and its… Using age-related mortality data for 40 countries, it is shown that the rate of aging does not change significantly over history and is almost the same for different countries from…
	Mortality attributable to influenza, evidence and… In the last recent years, before the Covid-19 pandemic, influenza-attributable mortality has been impressive, in particular among elderly aged 65 years. A wide variability between different countries, seasons, and years…