Published Paper Review- “Recruitment of Brown Adipose Tissue as a Therapy for Obesity-Associated Diseases”.

Reference

Boss, Olivier and Stephen R. Farmer 2012. “Recruitment of Brown Adipose Tissue as a Therapy for Obesity-Associated Diseases” US National Library of Medicine: National Institute of Health. Accessed  April 10, 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356088/

http://ksj.mit.edu/sites/default/files/images/tracker/2009/brownadiposetissue.jp                                   http://www.nature.com/ncb/journal/v14/n12/images/ncb2642-f1.jpg

The article, “Recruitment of Brown Adipose Tissue as a Therapy for Obesity-Associated Diseases” was well informing as it sought to present data on the effective use of brown adipose  tissue in obesity and related diseases.

                       What is Brown adipose tissue?

According to the authors of the article, brown adipose tissue is a flexible tissue that can be recruited by stimuli, and deteriorates in the absence of a stimulus. Its has a major contribution in cold-induced non-shivering thermogenesis and body weight homeostasis in animals ana is closely related to UCP1.

What is UCP1?                                                                                                                                                                                                       Thermogenin or uncoupling protein 1 ( UCP1) is an uncoupling protein found in the mitochondria of brown adipose tissue (BAT). It is used to generate heat by non-shivering thermogenesis. Non-shivering thermogenesis is the primary means of heat generation in hibernating mammals and in human infants.

The efficacy of increasing brown adipose tissue (BAT) recruitment (BAT mass and expression of UCP1) as a therapeutic approach for obesity and type 2 diabetes has been researched by many groups throughout the past 20 years.

Studies with rat specimens showed that agents which increase brown adipose tissue recruitment can effectively treat obesity and diabetes. In lean animals with normal brown adipose tissue amounts, enhancement of BAT recruitment or activity by drugs or cold exposure has no effect on body weight. While in obese animals, enhancement of energy spending by BAT recruitment is effective in decreasing body weight and improving metabolic status. Earlier results showed that over expression of UCP1 in white adipose tissue (WAT) of mice can prevent the development of obesity in genetic as well as dietary forms of diabetes. In contrast, lack of BAT or UCP1 stimulates obesity and diabetes in mice.

Some drugs were tested and it was revealed that induction of brown adipocyte formation with drugs in humans, in order to enhance or restore healthy levels of BAT recruitment, is possible to enhance energy expenditure.

                                
Brown adipose tissue and white adipose tissue.

Studied also showed that primary preadipocytes isolated from white and brown adipose depots demonstrate in vitro (in an artificial environment outside the living organism) differentiation  into white and brown adipocytes. There were many hypotheses that showed in WAT depots, brown adipocytes can emerge from differentiation of brown adipocyte precursors or preadipocytes or by transdifferentiation of the existing white adipocytes. It was shown that hyperleptinemia in rats induces the transformation of white adipocytes into so-called post-adipocytes (or fat-oxidizing machines), which have the phenotype of brown adipocytes. Several other effectors enhance brown adipocyte recruitment in white depots like synthetic PPARγ ligands. Brown adipocytes within the interscapular BAT depot of mice share an origin with skeletal myocytes that arise from the dermomyotome.

It is conceivable; therefore, that recruitment of WAT brown adipocytes is due to a selective activation of mural cells to progress along a brown lineage in response to effectors that are activated by the recruitment-associated stimulus. Possible effectors include BMP7, which has been shown to induce the conversion of mesenchymal stem cells to brown adipocytes in culture and is required for BAT formation in mice.

Infrared thermography provided data and proved that adult humans possess functional BAT that is activated by ephedrine.

The research showed that BAT can be recruited in humans just as in animals. Hence, brown adipose tissue could play an important role in human energy balance and body weight homeostasis and thus, has revived a concept that BAT is a therapeutic target for combating obesity-related metabolic disorders as there formerly existed a problem in identifying drug targets for brown adipocyte.

Studies found that stroma-vascular cell preparations from human BAT contained only very limited quantities of cells that can differentiate into brown adipocytes. Human brown adipocyte stem or progenitor cells, CD34+ are present in skeletal muscle and hMADs in subcutaneous WAT. These cells have self-renewal capability,  differentiate, in response to specific agents, into functional brown adipocytes and are rich in mitochondria. These cell types are thus quite distinct, and each have the potential of generating relevant cell models for studying human brown adipocyte biology as well as screening for anti-obesity therapeutics. Such screens could identify agents that induce the differentiation of the cells into brown adipocytes.

Analysis of several functional features of BAT include quantitative phenotypic cellular screens, PCR, western blot analysis of brown-selective genes and measurement of cell respiration to determine the degree of uncoupling of oxidative phosphorylation.

Authors found that defective recruitment or activity of brown adipose tissue may contribute to weight gain and insulin resistance. The metabolic activity and energy expenditure, thermogenesis, in humans is activated by cold. The amount of BAT inversely correlates to body weight and is independent of age.

Brown adipocyte stem cells are present in skeletal muscle and subcutaneous WAT of humans. This suggests that enhancing BAT recruitment to restore BAT mass to a healthy level, is practicable.

The investigations supported the contention that activation of BAT formation in obese individuals is therapeutically powerful. We also propose that enhancement of brown adipocyte functions in white adipose tissue (WAT) will also regulate energy balance as well as reduce insulin resistance in obesity-associated inflammation in WAT.

Investigations proved that resistance to obesity and other related disorders in various rodent models resulted from increased BAT mass and the number of brown adipocytes or UCP1 expression. Readily accessible brown adipocyte stem/progenitor cellsthrough biopsy of human tissues encourages the development of transplantation procedures to treat obese and diabetic patients. The implants in mice proved to advance the metabolic condition of obese, insulin resistant mice. In addition, brown adipocytes have beneficial effects on glucose metabolism, insulin sensitivity and overall energy balance. we looked at the  mechanism through which BAT affects the “adipostat.” BAT is quite different from WAT as BAT expresses significantly lower levels of resistin and other adipokines associated with insulin resistance.

Diagram showing the recruitment of brown adipose tissue.

In simpler words…brown adipose tissue helps adults burn more calories than white adipose tissue!!!

The most promising strategy for developing therapeutics for obesity and specifically, type two diabetes is to increase BAT mass. This allows the development of effective drugs for obesity, diabetes, and the metabolic syndrome that have very little side effects.

       

Published Paper Review- “Artificial Sweeteners: A systematic review of metabolic effects in youth.”

Reference

Brown, Rebecca J, Mary Ann De Banate, and Kristina I. Rother. 2010. “Artificial Sweeteners: A systematic review of metabolic effects in youth.” US National Library of Medicine: National Institute of Health. Accessed  March 20, 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951976/

The many processed snacks and soft drinks we so regularly purchase and consume contain so many additives we are unaware of. Haven’t you all ever stopped and wondered what these chemical additions can do to our bodies?

As we all may have noticed, obesity is becoming a serious problem in modern societies. Researsh on diseases have shown a relationship between the use of artificial sweeteners and weight gain.

FDA approved artificial sweeteners include acesulfame-K, aspartame, neotame, saccharin, and sucralose. In addition, a new sugar substitute called stevia, is recognized as “safe”.

Human and animal models provide evidence that artificial sweeteners participate in an active role in the gastrointestinal tract. Sweet-taste receptors, and taste receptors T1R family and α-gustducin, respond to artificial sweeteners, such as sucralose (Splenda) and acesulfame-K. Consumption of an artificial sweetener as well as food or drink containing sugar can lead to rapid sugar absorption, and increased insulin and GLP-1 secretion.

Beverages have been identified as a major source of artificial sweeteners in the diet. Estimates of artificial sweetener consumption are based on artificially-sweetened drinks.

It is important to examine possible contributions of these common food additives to the global rise in pediatric obesity and diabetes.

The review of pediatric studies on the effects of artificial sweeteners on weight gain and glucose metabolism recognized the existence of an association between artificially-sweetened beverage consumption and weight gain in children. A total of eighteen studies were analyzed as summarized below.

Review of pediatric studies on the effects of artificial sweeteners on weight gain and glucose metabolism.

Study	Subjects	Age	Duration	Result
Acute effects on food intake
Anderson et al. (48)	20 healthy children	9–10 years	–	6% compensation* in ad lib lunch intake 90 min after aspartame vs. sucrose-sweetened preload.
Bellissimo et al. (45)	14 boys	9–14 years	–	94% compensation in ad lib lunch intake 30 min after sucralose vs. glucose-sweetened preload.
Bellissimo et al. (44)	14 boys	9–14 years	–	112% compensation in ad lib lunch intake 30 min after sucralose vs. glucose-sweetened Kool-Aid preload (only 66% compensation if watching TV during lunch).
Birch et al. (49)	18 children	3–5 years	–	90% compensation in ad lib snack intake 20 min after aspartame vs. maltodextrin-sweetened pudding. When subsequently given intermediate caloric density pudding, children who previously had aspartame-sweetened pudding ate 50 kcal more ad lib snack than those previously given maltodextrin-sweetened pudding.
Birch et al. (46)	22 children	2.5–5 years	–	Children showed 109% compensation in ad lib snack intake 20 min after aspartame vs. maltodextrin-sweetened pudding, while adults showed 0% compensation.
	26 adults	25–35 years
Birch et al. (47)	24 children	2–5 years	–	60%, 1% and 11% compensation in ad lib snack intake 0, 30 and 60 min after aspartame vs. sucrose-sweetened preload. Children reduced ad lib snack intake 30 min after aspartame-sweetened preload (compared with water), but not after 0 or 60 minutes.
Interventional studies: randomized controlled trials
Knopp et al. (56)	55 children and young adults	10–21 years	13 wk	No significant differences in weight loss between 2.7 g/day encapsulated aspartame vs. placebo
Ebbeling et al. (57)	103 children (56♀ 47♂)	13–18 years	25 wk	No significant difference in BMI between those in intervention (replacing SSBs with ASBs) vs. control group except among heaviest subjects
Williams et al. (3)	32 overweight girls	13.2±1.4 years	12 wk	No significant difference in BMI between those permitted sugar-sweetened soda vs. those only artificially-sweetened soda
Observational studies: cross-sectional studies
Forshee et al. (52)	3 311 children (1 624♀ 1 687♂); USDA CSFII 1994–6, 1998	6–19 years	–	BMI positively associated with ASB consumption
Giammattei et al. (53)	385 children (199♀ 186♂)	11–13 years	–	Higher BMI z-score in those consuming ≥3 servings per day of SSBs and ASBs
O’Connor et al. (54)	1 160 children (581♀ 579♂); NHANES 1999–2002	2–5 years	–	No association between ASB consumption and BMI
Observational studies: prospective cohort studies
Ludwig et al. (55)	548 children (263♀ 285♂); Planet Health Project	11.7±0.8 years	2 yr	Obesity positively associated with SSB intake but negatively associated with ASB intake
Berkey et al. (50)	11 654 children (6 636♀ 5 067♂); Growing Up Today study	9–14 years r	3 yr	ASB intake associated with weight gain in boys, but not in girls
Blum et al. (43)	166 (92♀ 74♂)	9.3±1 years	2 yr	Increased ASB intake associated with BMI z-score at end of study
Striegel-Moore et al. (41)	2 371 girls	9–10 years	10 yr	Diet soda intake significantly associated with total daily energy intake
Johnson et al. (51)	1 203 children	5–7 years	9 yr	ASB consumption associated with baseline BMI and fat mass at age 9
Kral et al. (42)	177 children	3–6 years	3 yr	No association between ASB consumption and obesity risk status

^*Compensation after a preload is defined as the difference in subsequent ad libitum caloric intake between two conditions, divided by the calories in the preload.

BMI: Body mass index; SSB: sugar-sweetened beverage; ASB: artificially-sweetened beverage; USDA CSFII: United States Department of Agriculture Continuing Survey of Food Intake by Individuals; NHANES, National Health and Nutrition Examination Survey.

(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951976/table/T2/)

Studies like the National Health and Nutrition Examination Survey (NHANES) and the San Antonio Heart Study, showed positive connection between artificial sweetener use and increase in weight and BMI.

Are the recommendations for the use of artificial sweeteners appropriate?

To consume artificial sweeteners is the individual’s decision. Some are concerned about their weight and choose these in order to reduce their caloric intake. In the case of children, the decision is usually made by parents.

The effect of caloric versus artificial sweetener preloads on successive ad libitum, “at one’s pleasure” food intake in children were investigated by Birch et al. and Bellissimo et al. as shown in the previous table.

Studies showed that caloric compensation is more complete in children. The timing of artificial sweetener consumption with respect to meals may also affect food intake along with the child’s age and several other experimental circumstances. Generally, the effect of chronic consumption of artificial sweeteners on food intake was also explored by Birch et al. and with each trial children showed complete caloric compensation for the preload.

One study showed that overeating can be caused by associations of sweet taste with low caloric density.

The majority of pediatric studies found a positive correlation between weight gain and artificially-sweetened beverage intake. It was found that artificially-sweetened beverage consumption basically correlated both with baseline BMI and fat mass in children and that diet soda consumption was associated with higher daily caloric intake, not BMI.    

Other studies have established association between artificially-sweetened beverage use and adverse health effects. At present, only one study shows an inverse association between artificial sweetener use and weight gain.

Increased diet soda consumption was associated with decreased incidence of obesity.

Three interventional studies of artificial sweeteners and weight gain in children were conducted in children, and failed to show any metabolic effects.

Randomized controlled trials conducted in children found no association between the consumption of artificial sweetener and weight change. Currently, further studies on the effects of artificially-sweetened soft drinks on body weight in children and adults are ongoing, along with studies of the underlying mechanisms of the metabolic effects of artificial sweeteners.

The studies have not particularly shown the role of increased artificial sweetener use in obesity and diabetes and very little data on their in glucose metabolism in children are available.

These studies and similar research, will be significant in further understanding the role of artificial sweeteners in metabolic health.

What we do understand is that our body can become confused when we consume artificial sweeteners and thus we gain weight. In addition, artificial sweeteners are much more sweeter than sucrose (table sugar) and by consuming them we put our health at risk.

Although the longterm effects are unclear, studies have shown that there is indeed a  relationship between artificially sweetened beverage consumption and obesity especially in children, but the cause is not yet clear.

Do we really want to make ourselves “lab rats” by continuing careless use of these artificial sweeteners and suffer the unpredictable consequences?