Monday, January 7, 2013

20 Weeks of Gluttony Without Gaining a Single Gram of Visceral Fat? A Water Extract From Hops Made It Possible

Hops: More than an ingredient of the majority of OTC sleeping pills (photo LuckyStarr)
Hops beer made from the female flowers of Humulus lupulus was the (safer) alternative to untreated water in medieval Europe. Hops are the female flowers (also called seed cones or strobiles) of a hop species and are currently still used as a flavoring and stability agent in beer. Aside from that, the vigorous, climbing, herbaceous perennial has a longstanding history of medical uses and is probably best known for its sedative effects. That a hot water extract from hop could make an excellent addition to an anti-obesity and even fat loss regimen is yet news and - in view of its efficacy - even SuppVersity news ;-)

Eat like a pig, look like a goddess with hops!

Actually the subheading is pretty unfair, after all pigs don't eat much different from us, they are opportunistic omnivores... but this is no biology lesson, so let's get back to the topic at hand. There was a time, when I thought that 99% of us would eat crap all day, if it would not make us fat - well, unless I realized that I would not and that there are many others out there who don't even like crap (=convenience food) who would refuse to eat pizza, chips, fries, pancakes, ... all day long. That being said, imagine you could do just that or, if you were a rodent in a lab cage, gorge yourself on a high fat diet with 30% maize starch, 14% casein, 10% sugar, 5% cellulose, 4% soyabean oil, 32.5% lard and some minerals and vitamins (546 kcal/100 g diet - calorically and macrowise this looks much like chocolate and candy bars to me ;-) and end up not just exactly as lean, but even a little leaner than your peers on a "healthy" after two years of gluttony? Sounds crazy? Yeah, but it worked!

In the latest study from the Ehime University Graduate School of Medicine in Japan (Sumiyoshi. 2013), the scientists demonstrated that 20 weeks on the previously described high fat diet (if you use the rule of thumb that a mouse year equals 40 human years this would be the aforementioned 2 years).
Figure 1:Body weight trajectory and micrographs of the adipose tissue (Sumiyoshi. 2013)
Not being fat on the outside and, even more, having a regular weight on the scale is yet only the superficial clue to a more subtle, yet highly important internal difference: the fat cell size. With the hop extracts ability to inhibit lipid accumulation within adipose tissue cells by down-regulating our new acquaintance PPAR-gamma (see "PPARs - High or Low? How Are They Supposed to Be?", red box) and thus blocking both their expansion and their proliferation, the mice in the male C57BL/6J and Balb/c mice in the hop extract groups did in fact end up with less visceral body fat than their peers on the regular chow:
Figure 2: Organ weights (rel. to group on standard chow) and blood glucose clearance in OGGT (Sumiyoshi. 2013)
And if that's not enough as far as good news are concerned, their insulin sensitivity and ability to clear glucose from the blood stream was not compromised, either. In this context, it is also worth mentioning that the hop water extract had no effect on faecal fat excretion in mice fed a HF diet (in vivo), and pancreatic lipase activity (in vitro). In other words, the remarkable results were not simply the result of an inhibition of fat absorption.

Do you remember Rhein the natural PPAR-gamma antagonist in Rhubarb? No? Then I suggested you go back in the archives and (re-)read the respective article. You will be surprised how similar the results were... a total amelioration of the HFD induced weight gain, normal body fat levels and no insulin resistance - sounds familiar, no?
Bottom line: So, just as the scientists point out in their discussion of the results, the main mechanism behind this miraculous anti-obesity effects is the suppression of the HFD induced increases in PPAR-gamma activity. Against that background it appears ridiculous that already overweight, often obese diabetics and pre-diabetics are still treated with thiazolidinediones including pioglitazone and rosiglitazone (all PPAR-gamma agonists), which 'improve' insulin sensitivity by allowing the adipose organ to proliferate via adipocyte differentiation and increases in lipid and glucose uptake, and fatty acid storage.

According to the researchers, "[e]xperiments are now in progress to isolate the active substance(s) of hop extract". However, we all know that once this substance is found, the "logical" (actually this is business, not real logic) next step is to add a twist that turns it into a patentable not naturally occurring molecule and make counterproductive and (business logic) no longer really profitable PPAR-gamma agonists with another drug.

  • Sumiyoshi M, Kimura Y. Hop (Humulus lupulus L.) extract inhibits obesity in mice fed a high-fat diet over the long term. Br J Nutr. 2013 Jan;109(1):162-72.