No time except for...

...finishing my project. I have to present a draft of my thesis research on January 16th, so I dont have much time to read any paper not related to it.

After that, hopefully I will be able to finish a few pending posts. 

Happy holidays!

Getting fat: the type matters

Traditionally, increased fat mass has been viewed as unhealthy irrespective of the distribution of body fat. With increasing research on the subject, most researchers agree that increased visceral adipose tissue (VAT) is the main determinant of the metabolic disorders associated with obesity, compared to increased subcutaneous adipose tissue (SAT). 

In the last months, there has been a not-so-scientific debate on whether being fat eating a "healthy" diet is better than being thin eating a Western diet. One can be healthy even with an increased body fat mass? Is gaining fat with a given diet different than with another diet?

A study done by Tran et al. (1) caught my attention and motivated me to dig a little further in this topic. The authors found that transplantation of SAT and VAT to the subcutaneous or visceral regions of recipient mice produced remarkable differences on glucose homeostasis, weight and body fat gain. The scheme utilized for the transplants is shown below:

Copyright © 2008 Elsevier Inc. All rights reserved.

The most important effect was noticed in SC-VIS mice, which were transplanted with SAT into the visceral cavity. Compared to other mice, the rate of body weight gain (fat was transplanted "on top" of endogenous adipose tissue) was significantly lower, gaining on average only 63% and 59% (they used two cohorts) of the amount gained by sham-mice at the end of the study. This was irrespective of calorie intake, energy expenditure or heat production. Basal plasma glucose levels were reduced by 15% and plasma insulin levels were reduced by 33% in SC-VIS mice. Compared to sham, SC-VIS mice had 70% lower plasma leptin levels, but adiponectin was also decreased. Intraperitoneal glucose tolerance tests showed that SC-VIS mice had the lowest glucose levels, and insulin sensitivity (assessed by hyperinsulinemic-euglycemic clamp) was higher in this group. Glucose uptake in endogenous SAT was increased in both groups of mice transplanted with SAT, reflecting an increase in insulin sensitivity. Finally, gene expression of adiponectin, resistin and leptin levels were decreased in SC-VIS mice, compared to sham. 

Overall, the study findings were:

• Transplantation of SAT into the visceral cavity produced the most significant results in terms of weight gain, glucose tolerance and adipocytokine levels.
• SC-VIS mice had decreased body weight, decreased body fat percentage, increased percent of lean mass, without significant changes in total energy expenditure or heat production.
• Transplantation of SAT into recipient mice improved insulin sensitivity in the liver and in endogenous SAT. 
• Transplantation of SAT into the visceral cavity decreased average adipocyte area by 38% compared to endogenous SAT, and did not increase the adipocyte's size to that of the endogenous VAT. 
• Adding SAT to the visceral cavity reduced mRNA levels of resistin, leptin and adiponectin, compared to endogenous SAT.

These results suggest a "protective" role of SAT in obesity. There is evidence that insulin resistance correlates with VAT, regardless of bodyweight (2). VAT appears to produce more IL-6 than SAT (3), which correlates with increased macrophage infiltration in VAT compared to SAT (4). Liposuction, despite reducing bodyfat levels, does not improve metabolic markers in the short and long term (5), does not improve insulin sensitivity of muscle, liver or adipose tissue; and doesn't affect levels of C-reactive protein, IL-6, TNFa and adiponectin in diabetic or normal subjects (6). Accordingly, SAT seems to modulate TNFa expression in VAT (7). 

Thus, it seems that it is not weight lost per se which is important for preventing metabolic damage, but the type of body fat lost. Liposuction achieves equal or greater weight loss than lifestyle modifications, but fails to improve metabolic parameters. 

Effect of different diets on body fat distribution

From the above discussion, it is reasonable to think that the best diet is the one that a. decreases body fat mass and b. reduces and/or redistributes fat mass towards SAT.

Active rats fed a ketogenic diet show increased SAT compared to matched carbohydrate-fed rats (8), despite similar body fat levels, although there are contradictory results (9). Weight loss produced either by a high fat-low carbohydrate diet or a low fat-high carbohydrate diet show the same effects on both SAT and VAT (10), suggesting that the macronutrient ratio is not important. This contrasts with a small study which showed that the visceral to subcutaneous fat ratio (V/S) decreased only in the low carbohydrate group (11), compared with the group eating a high carbohydrate diet, even when both diets were hypocaloric. Other authors suggest that ketogenic diets decrease VAT more significantly than high carbohydrate diets (12), although the method used to estimate VAT levels (DEXA) has some predictive problems (13). 

Chaston and Dixon (14) have proposed that acute caloric restriction produces a preferential loss of VAT in the short term and that this effect is seen with modest weight loss. Alternate day fasting (ADF) has also shown to improve body fat distribution in mice, increasing the proportion of SAT vs. VAT and levels of adiponectin, and reducing the levels of leptin and resistin (15, 16). These effects seem to be independent of the diet and body fat loss.

Summing up

Independent of total body fat, there seems to be a protective effect of SAT vs. VAT. This might be the reason why not all obese people develop metabolic syndrome or insulin resistance (17), as healthy obese subjects seem to have less risk for complications than normal-weight subjects with metabolic syndrome (18). Calorie restriction seems to be the most important factor for preventing an increase in VAT, while ADF might provide an additional benefit without weight loss. From the above, we can try to answer the questions proposed: 

One can be healthy even with an increased body fat mass? 

Yes, given a proper body fat distribution (higher proportion of SAT vs. VAT).

Is gaining fat with a given diet different than with another diet?

Possibly. Overfeeding studies done do not control for macronutrient composition, so there is no evidence of a different effect of different diets. However, from the studies available, gaining body fat while implementing ADF might be different than with a Western diet. Moreover, specific nutrients might have different effects regardless of body fat gain, such as fructose (19), although recent evidence do not show adverse effects of overfeeding fructose on visceral fat (20). In either case, having a normal-weight is not protective for cardiometabolic abnormalities (21). This suggests that dietary habits are important even in the absence of weight gain (normal-weight obesity), and that gaining weight with a healthy diet might not be as detrimental as gaining weight with a Western diet.

Tran TT, Yamamoto Y, Gesta S, & Kahn CR (2008). Beneficial effects of subcutaneous fat transplantation on metabolism. Cell metabolism, 7 (5), 410-20 PMID: 18460332