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