When you stop to think about which bits of you are most valuable – you probably think of the brain first, followed by the heart second. The rest of the list will vary according to your own particular idiosyncrasies. The organ that is least likely to make it onto the list, is the liver.
The liver flops at marketing
The liver is “everything” – it is the organ that controls ALL metabolism and is involved in the production of a host of chemicals, including fat.
Most people never give it a second thought, unless they upset it during an alcoholic binge. It is remarkably resilient to the stresses and strains placed on it by living in our “chemical world” and it ultimately controls your entire metabolism.
Disruptions in the liver result in metabolic syndrome, the scourge of modern living.
Your liver is your fat factory
Fat production by the liver runs on a 24 hour cycle, the circadian rhythm. Production typically happens at night. To keep the factory ticking over requires different sets of workers. The liver employs a day shift and a night shift, in the form of different groups of enzymes.
The night shift is when production is in high gear and molecular workers labour to keep the fat rolling off the production line. The day shift, is typically a skeleton staff, concentrating on maintenance, with minimal production taking place.
Hiring the right staff in the fat factory
Managing the fat production facility means making sure that “the right” staff, have the “right” equipment at the “right” time. The liver’s management team consists of two chemicals – one is called Rev-erb (nuclear receptor) and the other, is histone deacetylase 3 (HDAC3).
HDAC3 and Rev-erb keep a tight schedule
At 5 pm, HDAC3 is found in 15 000 places in the liver genome, effectively opening the factory doors. HDAC3 does this by rearranging the protein scaffold surrounding the genome. Once the door is open, Rev-erb then drops off the molecular workers at genes that are involved in fat metabolism.
By the time the sunrises, the construction team are heading off for a well earned snooze, effectively halting fat production for the day. At 5 am, HDAC3 is only found in 100 places in the liver genome.
If Rev-erb or HDAC3 aren’t on time, all hell breaks loose in the factory
If either of these guys fails to turn up for work on time, the fat factory turns chaotic, resulting in continuous fat production as the day and night shift workers follow their own schedule. The scenario is a bit like what happens when the cat is a way – the mice WILL play.
The untamed fat production quickly leads to an accumulation of fat in the liver, known as non-alcoholic fatty acid disease. Blobs of fat lying everywhere, make the liver a tough place to work and metabolic activities in the liver start to slip, bringing on metabolic syndrome.
Proper staff management keeps fat production under control
Fat production requires a workforce that clocks in and out like clock work i.e. it follows the circadian rhythm. So to keep your fat production in check, you need to watch the clock on the wall as well. Failure to get enough sleep, at night, causes chaos in the liver leading to obesity, diabetes and cardiovascular disease.A Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism. Science 331(6022): 1315-1319. Dan Feng, Tao Liu, Zheng Sun, Anne Bugge, Shannon E. Mullican, Theresa Alenghat, X. Shirley Liu, and Mitchell A. Lazar.
Interested in finding out more about the on and off buttons of fat metabolism ?
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