With a steadily increasing incidence, obesity has become the leading medical disorder of the 21st Century. In particular, the middle-aged population appears to be prone to obesity. Although the reasons for this remain largely enigmatic, several factors are strongly implicated in the development of obesity, such as sedentary lifestyle and poor dietary habits. Genetic factors have also been suggested to control age-dependent obesity. For example, hypothalamic pro-opiomelanocortin neurons, which are involved in the regulation of food intake, are progressively silenced during aging.
Most of the knowledge on fat development stems from experimental studies in which white adipose tissue (WAT) expansion occurs rapidly upon high-fat diet (HFD) feeding. The mechanisms involved in progressive WAT expansion during aging, however, remain mostly unidentified. Because obesity at a later age predisposes to life-threatening conditions such as insulin resistance, type 2 diabetes, and cardiovascular disease, understanding the causal molecular mechanisms of age-related obesity may provide a strategy for treating these disorders.
One of the hallmarks of aging is the functional dysregulation of mitochondria, which constitute the central metabolic hub in many cell types and are the gateway to aerobic metabolism. Mitochondrial oxidative phosphorylation is governed by the electron transport chain (ETC). Oxygen is the final electron acceptor in the ETC, and cytochrome c oxidase (complex IV [CIV]), the terminal enzyme of the ETC, reduces it to H2O after which energy is produced in the form of ATP by the action of ATP synthase.
In mature white adipocytes, mitochondria have a central role in many processes, such as ensuring energy generation through fatty acid β-oxidation in the mitochondrial matrix. Aside from ATP production, mitochondria generate the necessary metabolic intermediates for lipid synthesis, thereby determining lipogenic potential. Moreover, mitochondrial activity in WAT is associated with the release of several adipokines, including adiponectin.
Aging has also been associated with increased adiposity early in the lives of mice and humans. However, it is unclear whether mitochondrial dysfunction in WAT contributes to age-related adipocyte enlargement and whether it can be restored to counteract age-dependent WAT expansion.
Researchers in the journal Cell Reports show that adipocytes of early middle-aged mice already exhibit mitochondrial dysfunction, which is largely associated with a decline of mitochondrial CIV activity and assembly. This decline in CIV activity involves a hypoxia-inducible factor 1A (HIF1A)-dependent reduction of CIV components, including cytochrome c oxidase subunit Vb (Cox5b).
Silencing of Cox5b is sufficient to promote a global decline of CIV assembly, as well as decreased fat oxidation, and contributes to adipocyte enlargement during aging. Conversely, in vivo restoration of COX5B expression counteracts age-dependent white adipocyte enlargement.
Collectively, these findings highlight the potential of targeting mitochondrial CIV to reverse adipocyte expansion during aging.
http://www.cell.com/cell-reports/abstract/S2211-1247(16)31105-6
Latest News
Wiring of the human neocortex
By newseditor
Posted 24 Apr
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Other Top Stories
Lipid nanoparticle-mRNA (LNP-mRNA) to treat liver failure
Read more
AI to predict cardiovascular risk
Read more
Aggravated multiple sclerosis from childhood trauma linked to beta-…
Read more
Common fronto-temporal effective connectivity in humans and monkeys
Read more
Reduced growth in boys with neonatal antibiotic use
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Harnessing gastrointestinal…
By newseditor
Posted 24 Apr
Sex-specific modulation of…
By newseditor
Posted 24 Apr
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar