Leptin, Living Environment and Cancer

Cancer is not only influenced by its micro-environment but also by a broader environment, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (see here).

In this study, the scientists showed that tumors (melanoma and colon cancer) of mice in an enriched housing (20 mice in large containers equipped with toys, hiding places and running wheels, along with unlimited food and water as compared to control group) were 80 percent smaller than those in control animals (5 in smaller, standard containers with no toys but with unlimited food and water) within six weeks. Almost 20 percent of the animals in the enriched group had no visible tumors at all. Control animals, on the other hand, all had visible tumors.

"The anti-cancer effect we observed in this study was not due simply to increased activity by the animals, but rather it was induced by social and physical challenges that are associated with the release of stress hormones from the adrenal gland.” said During, one of the authors.

The same effect can be mimicked by blocking leptin or by activating HAS (hypothalamic-sympathoneural-adipocyte) pathway, which in turn lower the serum leptin level.

Leptin is a hormone that is primarily produced in a type of fat tissue called white adipose tissue. The level of circulating leptin is directly proportional to the total amount of fat in the body, in another word, higher amount of body fat means higher amount of circulating leptin.

Leptin is a circulating signal that reduces appetite. The absence of a leptin (or its receptor) leads to uncontrolled food intake and resulting obesity. However, in general, obese people have an unusually high circulating concentration of leptin (1), leading to the conclusion that these people are resistant to leptin.

Fasting or following a very-low-calorie-diet, on the other hand, lowers leptin levels (2).

Studies published recently suggest that the consumption of high amounts of fructose causes leptin resistance and elevated triglycerides in rats. Rats fed high-fructose diet subsequently ate more and gained more weight than controlled rats fed a high fat, high calorie diet (3). In North America, consumer foods and products typically use high-fructose corn syrup as a sugar substitute. In the United States, it has become very common in processed foods and beverages, including soft drinks, yogurt, industrial bread, cookies, salad dressing, and tomato soup (4).

What does it all mean?

I always believed that obesity was not caused solely by over-eating. If anyone has ever been to Guangzhou, China, it is easy to see that people there eat a lot and still stay skinny. Therefore, it must be foods that we in North America repeatedly eat that people there do not eat (or the other way around) that is making us gain weight. Refined sugar is probably one of the foods.

(1) Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ & Bauer TL (1996). "Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans". N Engl J Med 334 (5): 292–295.

(2):
• Dubuc G, Phinney S, Stern J, Havel P (1998). "Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women". Metab. Clin. Exp. 47 (4): 429–34.
• Pratley R, Nicolson M, Bogardus C, Ravussin E (1997). "Plasma leptin responses to fasting in Pima Indians". Am. J. Physiol. 273 (3 Pt 1): E644–9.
• Weigle D, Duell P, Connor W, Steiner R, Soules M, Kuijper J (1997). "Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels". J. Clin. Endocrinol. Metab. 82 (2): 561–5.

(3):
• Vasselli JR (November 2008). "Fructose-induced leptin resistance: discovery of an unsuspected form of the phenomenon and its significance. Focus on "Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding," by Shapiro et al.". Am. J. Physiol. Regul. Integr. Comp. Physiol. 295 (5): R1365–9.
• Shapiro A, Mu W, Roncal C, Cheng KY, Johnson RJ, Scarpace PJ (November 2008).
“Frutose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295 (5): R1370–5.

(4) Warner, Melanie (July 2, 2006). “A Sweetener With a Bad Rap”. The New York Times.