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Grow More Fat and Improve Metabolic Health: Insights from TZD Treatment of Obese
Obesity Panacea ^ | November 16, 2009 | Peter Janiszewski

Posted on 12/29/2009 12:28:12 AM PST by neverdem

By now, readers of Obesity Panacea (which just celebrated its 1 year anniversary!) have hopefully learned that excess weight is not directly predictive of health risk, and that excess fat mass is not in itself unhealthy. Recall that approximately 30% of individuals who are classified as obese by their body weight turn out to be metabolically healthy, and in fact seem not to get much metabolic benefit (or may even get worse) when they lose weight. Also consider that individuals who have NO fat tissue (e.g. lipodystrophy) have extremely elevated metabolic risk factors, meanwhile others who can apparently indefinitely grow more fat mass (multiple symmetric lipomatosis – think Michelin man) have metabolic profiles we’d all like to have.

The emerging theory of why obesity is associated with disease risk suggests that it is not the excess amount of fat that results in problems – but rather, it is the inability of the fat tissue (specifically subcutaneous, or under the skin fat) to expand enough to store all the excess calories being ingested. In other words, if obese and metabolically unhealthy individuals could somehow develop more subcutaneous fat tissue, they could theoretically become healthier.

That’s right – get fatter and yet healthier.

While these notions surely seem like heresy or simply void of logic to many of you reading, a study just published ahead of print in the journal Obesity, beautifully illustrates the theoretical argument I just described.

In the study, 12 overweight or obese and metabolically unhealthy subjects were given a drug (Pioglitazone) for a duration of 12 weeks. While the exact actions of this drug, and more generally the thiazolidinediones (TZD) class of drugs are beyond the scope of this post, it is important to understand that these drugs seem to upregulate the production of healthy new fat cells (a process known as adipogenesis) – that is they make you fatter. By doing so, these drugs increase the storage capacity of your fat tissue – something that is limited in unhealthy obese individuals.

And that is precisely what happened in these subjects following 3 months of Pioglitizone administration. First, they gained about 2kg of body weight. Their amount of subcutaneous fat in the belly went up by about 10% and that in their butt/thigh by about 24%. Interestingly, their amount of dangerous visceral fat decreased by about 11%. (Some suggest that visceral fat really begins to accumulate and potentially lead to metabolic problems when benign subcutaneous fat runs out of storage space. Thus, not surprising to see an increase in storage capacity of subcutaneous fat and yet a reduction in visceral accumulation).

Also, a fat biopsy from the belly of the subjects showed that the increase in fat mass was due to an increase in the number of small and healthy adipocytes (fat cells) which are better able to take up more circulating fat.

Alright, so people with excess fat and metabolic problems took drugs for 12 weeks which apparently made them fatter, and what happened to their insulin sensitivity (a major metabolic marker of diabetes risk)?

Their insulin sensitivity improved by over 28%!

That’s right – they got fatter and yet healthier.

Interestingly, the authors were able to show a close correlation between the relative increase in new subcutaneous fat cells and insulin sensitivity – the more new fat cells a subject developed, the more their insulin sensitivity improved.

Still believe the “fat is bad” mantra? As this study illustrates, matters related to excess fat and health risk are much more nuanced than what many would have you believe.


TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: adipogenesis; obesity; pioglitazone; tzd
Pioglitazone Increases the Proportion of Small Cells in Human Abdominal Subcutaneous Adipose Tissue
1 posted on 12/29/2009 12:28:13 AM PST by neverdem
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To: austinmark; FreedomCalls; IslandJeff; JRochelle; MarMema; Txsleuth; Newtoidaho; texas booster; ...
Thiazolidinediones (TZDs) are insulin sensitizers. They're only for type IIs. IMHO, this might give some insights in physiology.

FReepmail me if you want on or off the diabetes ping list.

2 posted on 12/29/2009 12:44:05 AM PST by neverdem (Xin loi minh oi)
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To: neverdem

“Hopefully.” Ugh.

“One-year anniversary.” Ugh.


3 posted on 12/29/2009 1:22:39 AM PST by Arthur McGowan (In Edward Kennedy's America, federal funding of brothels is a right, not a privilege.)
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To: neverdem
Score!


Frowning takes 68 muscles.
Smiling takes 6.
Pulling this trigger takes 2.
I'm lazy.

4 posted on 12/29/2009 2:55:51 AM PST by The Comedian (Evil can only succeed if good men don't point at it and laugh.)
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To: neverdem

But what determines a person’s distribution between subcutaneous and visceral fat? Is this something a person can impact by diet or what?


5 posted on 12/29/2009 2:18:49 PM PST by fightinJAG (Mr. President: Why did you appoint a bunch of Communists to your Administration?)
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To: fightinJAG
But what determines a person’s distribution between subcutaneous and visceral fat? Is this something a person can impact by diet or what?

Diet and exercise has the most effect on visceral fat, IMHO.

The subcutaneous fat (panniculus adiposus) serves many functions, including insulation; reservoir for fluids, electrolytes, and energy; and shock absorber.

Visceral fat is stored energy. IIRC, your heart can use free fatty acids for energy. Some fat is the last to go in starvation such as fat in the cheeks of POWs.

6 posted on 12/29/2009 3:10:18 PM PST by neverdem (Xin loi minh oi)
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