CCMB: Can alpha chain of clusterin protein control weight, fat gain in animals?

T Ramakrishna_Ch. Mohan Rao_M.Suvarsha Rao-Optimized-1

Dr. Ramakrishnan (left), Dr. Mohan Rao (centre) and Suvarsha Matukumalli studied rats injected with beta chain and found fat accumulation from day two onwards.

The two chains of clusterin protein, which are normally expressed in several tissues and can be found in several body fluids, when present together tend to lower lipid levels but administration of one of its chains — alpha or beta — results in completely different outcomes. Cells treated with a recombinant beta chain tend to accumulate fat while cells treated with an alpha chain showed no increase in lipid accumulation. Rabbits administered with a recombinant beta chain showed nearly 40% increase in weight while animals given an alpha chain showed no such increase. The results were published in the journal Scientific Reports.

“Two chains of clusterin when present together tend to decrease body weight but one of the two chains (beta clusterin) increases body weight. This is quite unusual,” says Dr. Ch. Mohan Rao from the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, and the corresponding author of the paper. “So the alpha chain should ideally be compensating for increase in body weight. But the alpha chain does not do that.”

Rats gained lean mass not fat

“While excess energy gets accumulated in the form of fat when beta chain was injected into rats, we did not see this in the case of alpha chain. One possibility is that the alpha chain helps in the metabolism of food in such a way that fat does not accumulate,” he says. “Dissected rats that were given alpha chain showed increased levels of lean mass.”

Apparently, there was no difference in the food intake between animals treated with alpha or beta chain. “It means that weight increase can happen even when there is no increase in food intake. It is the energy management by the body that is important. And alpha chain seems to modulate metabolism in such a way to promote energy expenditure and thus prevent fat accumulation,” he says.

The effect of alpha and beta chains were tested on myoblast cells, fibroblast and cancer cells. The individual chains were injected into rabbits as well. “In my lab we study the effect of small heat shock protein on health and disease. To raise antibody for clusterin we injected the chains separately into rabbits. One set of rabbits was gaining weight while the other did not. That’s when we investigated the reasons. The animal-house in-charge noticed the change in the animals,” recalls Dr. Rao.

Rats too gained weight

Though the effects of the two chains were seen in rabbits, the researchers turned to rats as more animals were required for investigating the effect of individual chains on animals.

“We could see fat accumulation in cells from day two onwards. We observed for 10 days and fat accumulation continued for all the 10 days; we could study cells continuously only for 10 days,” says Suvarsha Rao Matukumalli from CCMB and the first author of the paper. “In the case of animals injected with beta chain, fat accumulation continued for four-five months. The controls and animals given alpha chain did not show weight or fat gain.”

When cells were administered both the chains simultaneously, the cells did not accumulate fat for two-three days but started thereafter. “Fat accumulation was not as much as when only the beta chain was given but fat accumulation nevertheless continued,” says Ms. Matukumalli. But the effect of both the chains in animals was quite different. “When we introduced both alpha and beta chains together in animals we did not see any weight gain. The animals were very much like the controls,” she says. “Only large-scale, in-depth studies can reveal if alpha chain prevents weight gain.”

Published in The Hindu on March 19, 2017

Where does the fat go when you lose weight?


Lungs are the primary excretory organ for weight loss. – Photo: R. Prasad

Many won’t know the answer to this question and there is no reason to feel embarrassed as general practitioners, dietitians and personal trainers themselves were not sure of the answer.

A study undertaken by two researchers and published in the journal BMJ found widespread misconception about the fate of fat among doctors, dietitians and personal trainers.  The misconceptions ranged from “fat is converted to energy or heat, metabolites of fat are excreted in the faeces or converted to muscle.” Nearly 70 per cent of 50 doctors and 50 dietitians thought fat is converted into energy, which violates the law of conservation of energy.

The correct answer is: lungs are the primary excretory organ for weight loss!

Let’s see how this is true. We know excess carbohydrate and protein consumed are converted to triglyceride and stored in fat cells (adipocytes).  When more energy is used than consumed, the body dips into the fat reserve to release energy. Biochemically speaking, the triglycerides stored in the fat cells are metabolised when we lose weight.

The fat cells release more triglycerides when energy expenditure is more than energy intake and results in fat cells shrinking in size.  But the fat cells never completely disappear and that is the reason why they easily bulge in size when energy intake is more than energy spent.

The triglycerides are metabolised by combining with oxygen. Broadly speaking, the process can be summarised as:

Triglyceride (C55H104O6) + 78O2 → 55CO2 + 52H2O + energy

Though energy is also produced when fat is burned, the proportion of carbon dioxide and water produced is much higher. According to the BMJ paper, when 10 kg of fat (triglyceride) is burnt, 8.4 kg of it is exhaled as carbon dioxide and 1.6 kg is lost as water.

Energy lost

Responses of a sample of doctors, dieticians, and personal trainers to the question “When somebody loses weight, where does it go?” (Correct answer CO2). – Image: BMJ

“These results show that the lungs are the primary excretory organ for weight loss,” the paper notes. “The water formed may be excreted in the urine, faeces, sweat, breath, tears or other bodily fluids.”

Ruben Meerman, a physicist and Australian TV science presenter and the first author of the paper lost 15 kilograms in 2013 and simply wanted to know where those kilograms were going. “After a self-directed, crash course in biochemistry, I stumbled onto this amazing result,” he told University of New South Wales.  “The fact that almost nobody could answer it took me by surprise, but it was only when I showed Andrew Brown, [head of the School of Biotechnology and Biomolecular Sciences, UNSW] my calculations that we both realised how poorly this topic is being taught.”

Lifting the veil on weight loss, the authors point out that a person weighing 70 kg spending a day asleep, at rest, and performing light activities would exhale 0.74 kg of carbon dioxide; the carbon lost from the body is 203 g.

By exercising for one hour such that his metabolic rate is seven times that of resting would allow the person to remove an additional 39 g of carbon. So the total carbon removed from the body works out to 240 g.

One of the most frequently asked questions the authors have encountered is whether simply breathing more can cause weight loss. The answer is no. Breathing more than required by a person’s metabolic rate leads to hyperventilation, which can result in dizziness, palpitations and loss of consciousness, notes a University press release.

Alas, eating a single 100 g muffin would meet 20 per cent of his daily energy requirement. “Physical activity as a weight loss strategy is, therefore, easily foiled by relatively small quantities of excess food,” they underline.