Leptin [was: More Popular Misconceptions]

[Guest guest]

An interesting piece of the puzzle; seems that high levels of

triglycerides prevent leptin from getting into the brain to turn off

feeding signals.

Seems reasonable that statins, affecting a modest decrease in

triglycerides as they do, might be a legitimate weight loss drug too?

http://diabetes.diabetesjournals.org/cgi/content/abstract/53/5/1253

http://snipurl.com/7o2a

Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier

A. Banks1, Alan B. Coon1, M. 1, Asif

Moinuddin1, M. Shultz1, Ryota Nakaoke1,2, and E. Morley1

1 Department of Internal Medicine, Division of Geriatrics, Geriatric

Research, Education, and Clinical Center, Veterans Affairs Medical

Center, St. Louis University School of Medicine, St. Louis, Missouri

2 Department of Pharmacology, Nagasaki University School of Medicine,

Nagasaki, Japan

Obesity is associated with leptin resistance as evidenced by

hyperleptinemia. Resistance arises from impaired leptin transport

across the blood-brain barrier (BBB), defects in leptin receptor

signaling, and blockades in downstream neuronal circuitries. The

mediator of this resistance is unknown. Here, we show that milk, for

which fats are 98% triglycerides, immediately inhibited leptin

transport as assessed with in vivo, in vitro, and in situ models of

the BBB. Fat-free milk and intralipid, a source of vegetable

triglycerides, were without effect. Both starvation and diet-induced

obesity elevated triglycerides and decreased the transport of leptin

across the BBB, whereas short-term fasting decreased triglycerides

and increased transport. Three of four triglycerides tested

intravenously inhibited transport of leptin across the BBB, but their

free fatty acid constituents were without effect. Treatment with

gemfibrozil, a drug that specifically reduces triglyceride levels,

reversed both hypertriglyceridemia and impaired leptin transport. We

conclude that triglycerides are an important cause of leptin

resistance as mediated by impaired transport across the BBB and

suggest that triglyceride-mediated leptin resistance may have evolved

as an anti-anorectic mechanism during starvation. Decreasing

triglycerides may potentiate the anorectic effect of leptin by

enhancing leptin transport across the BBB.

Address correspondence and reprint requests to A. Banks, 915

N. Grand Blvd., St. Louis, MO 63106. E-mail: bankswa@...

> The alleged fat gene was hypothesized from studies of obese mice.

> Mice that didn't receive a gene from either parent to make leptin

> were always hungry regardless of how much they ate and consequently

> ended up obese. Turns out that fat people make lots of leptin

> although they may not be as sensitive to it as thin folks due to

> increased fat mass....

> BTW, leptin is a protein that is only produced in fat tissue and

> plays an important role in insulin signalling.

>

> Cheers,

>

>