Leptin and Mood

The appetite-controlling hormone leptin has received a great deal of attention in the medical literature recently for its role in weight management, studies that are of interest to the 68 percent of American adults who are overweight.¹ However, surprisingly, this hormone has recently been studied for a less obvious role in health—an ability to regulate mood and well-being.

Interestingly, researchers found that, in addition to the hypothalamus, leptin receptors are also highly expressed in areas of the brain that control mood and emotions such as the hippocampus, cortex and amygdala. This led researchers to investigate the role that leptin plays in other physiological processes such as mood and behavior. Before we describe this interesting new connection between leptin and mood in detail, it’s important to provide a brief refresher course on the role leptin plays in weight management.

The Hunger Hormone

Leptin is a protein hormone synthesized from fat cells (adipocytes) encoded by the obese (ob) gene, and levels of circulating leptin are proportional to the amount of fat in the body. Leptin is of particular interest due to its ability to reduce appetite. However, obese individuals have elevated levels of leptin, suggesting they may be resistant to the effects of the hormone, similar to insulin resistance seen with type 2 diabetes. Sustained elevated leptin levels are believed to cause leptin desensitization in these individuals, thereby failing to trigger the sensation of satiety or fullness after eating.

Leptin functions by decreasing hunger and food consumption by inhibiting the synthesis and release of the neurotransmitter neuropeptide Y, which stimulates food intake. Healthy levels of leptin and leptin activity, in the absence of leptin resistance, increases energy expenditure by the cells, stimulating oxygen consumption and raising body temperature, resulting in loss of adipose tissue (fat) mass. Leptin acts primarily by binding to receptors in the hypothalamus, acting as a signal to the brain regarding current energy stores, thereby regulating energy homeostasis.

Leptin and Depression

Recent research has uncovered a connection between serum levels of leptin and the development of depression. In one study, researchers investigated the relationship between depressive disorder, the metabolic syndrome, leptin and adiponectin. Adiponectin is another protein hormone secreted from adipose cells that acts in concert with leptin, helping to sustain optimal lean body mass. In this study, 38 women with depressive disorder and 38 healthy women were evaluated for plasma leptin and adiponectin levels; insulin; C-peptide (the molecule that results from the activation of insulin from pro-insulin); and HOMA-IR, which is a measurement of insulin resistance. The study results showed that the depressed women had increased serum leptin levels compared to the healthy women. In addition, these depressed women had increased insulin, C-peptide, and HOMA-IR values of insulin resistance, and reduced levels of adiponectin compared to the control group. The researchers suggested that this finding may be the mechanism in which depression increases the risk of type 2 diabetes and cardiovascular disease.²

In another study, investigators evaluated serum leptin levels in 510 women between 20 and 78 years of age. The women were interviewed to evaluate the lifetime history of major depressive disorder or dysthymia (chronic mild depression). The women were also evaluated for body mass index (BMI) plus lifestyle and medication use. The results of the study showed that independent of the BMI, serum leptin levels were greater among women with a lifetime history of depression compared to women without any history of depression. In non-smokers, increased serum leptin levels also predicted subsequent development of depressive disorder over 5 years, even after controlling for BMI, medications or other lifestyle factors.³

A third study compared nocturnal excretion of leptin, cortisol, adrenocorticotropic hormone (ACTH) and growth hormone in depressed and healthy subjects. The results showed that nocturnal serum leptin was significantly higher in depressed subjects, despite reported weight loss. There was also a trend toward increasing nocturnal cortisol (stress hormone) secretion in the depressed subjects. Furthermore, this study showed that serum leptin was correlated with BMI in controls, but not in patients with depression, which suggests that leptin secretion is altered in depressed patients. The researchers proposed that increased cortisol in depression may counteract the reduction in leptin secretion caused by decreased food intake and weight loss.⁴

Similarly, another interesting study evaluated the serum leptin levels in subjects with seasonal affective disorder (SAD), which is a condition characterized by winter depression and is often accompanied by increased appetite, carbohydrate cravings and weight gain. The subjects were evaluated for depression, BMI and appetite during the summer and the winter. The study found that compared to healthy controls, the subjects with SAD had winter depression with increased appetite, caloric intake and carbohydrate craving. However, leptin levels did not change with changes in body weight in these subjects during the winter, suggesting a possible seasonal association with leptin sensitivity in individuals with SAD.⁵

Researchers have also evaluated leptin levels in stroke patients, who often suffer from post-stroke depression. The study showed that leptin levels were significantly higher in the stroke patients that suffered from post-stroke depression at hospital discharge or at one month after being discharged from the hospital when compared to the post-stroke patients without depression.⁶

Despite this research, there is also controversial evidence showing that leptin levels may be lower in some individuals with depression. One study compared serum leptin levels in patients with major depressive disorder, schizophrenic patients and healthy control subjects. In this study, 69 patients with major depressive disorder, 78 schizophrenic patients and 51 healthy controls were evaluated for serum leptin levels, cholesterol levels and BMI. The results showed that serum cholesterol and leptin levels were significantly reduced in the subjects with major depressive disorder and increased in the subjects with schizophrenia, compared to the healthy control subjects.⁷ Some researchers suggest that this discrepancy may be due to other influences on leptin levels such as age, sex, body mass status, and the presence of additional medical conditions.  Additionally, researchers propose that leptin insufficiency may only occur in a subpopulation of depressed patients.⁸ This is why it is important to concentrate on balancing leptin levels with adiponectin rather than focus on raising or lowering levels of leptin in response to symptoms.

Balancing Leptin Levels

A patented combination of high viscosity polysaccharides from acacia gum and esterfied fatty acids (as found in Leptin Control Formula) can be used to balance leptin and adiponectin. A study was conducted to evaluate the effect of this unique blend of high viscosity polysaccharides and esterified fatty acids on leptin and adiponectin concentrations. In this placebo-controlled, double-blind study, 22 women were supplemented with high viscosity polysaccharides and esterified fatty acids or placebo for 8 weeks while on a caloric restricted diet and performing cardiovascular exercise. The women were evaluated for serum leptin, adiponectin and insulin levels at the beginning of the study, during the study and after the 8 weeks of treatment. The study showed that the treatment group experienced significant reduction in leptin and insulin and an increase in adiponectin, as well as favorable changes in weight and percent body fat. Thus, high viscosity polysaccharides and cetylated (esterified) fatty acids effectively modified these hormones.⁹

Conclusion

Recent research has uncovered additional physiological activities for the hormone leptin beyond regulation of energy metabolism. Leptin, which has been shown to affect mood balancing, can be effectively modulated using a natural supplement comprised of high viscosity polysaccharides and esterified fatty acids combined with a diet and exercise regimen.

References

1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and Trends in Obesity Among US Adults, 1999-2008. JAMA. 2010;303(3):235-241.

2. Zeman M, Jirak R, Jachymova M, et al. Leptin, adiponectin, leptin to adiponectin ratio and insulin resistance in depressive women. Neuro Endocrinol Lett. 2009;30(3):387-95.

3. Pasco JA, Jacka FN, Williams LJ, et al. Leptin in depressed women: cross-sectional and longitudinal data from an epidemiologic study. J Affect Disord. 2008 Apr;107(1-3):221-5.

4. Antonijevic IA, Murck H, Frieboes RM, et al. Elevated nocturnal profiles of serum leptin in patients with depression. J Psychiatr Res. 1998 Nov-Dec;32(6):403-10.

5. Cizza G, Romagni P, Lotsikas A, et al. Plasma leptin in men and women with seasonal affective disorder and in healthy matched controls. Horm Metab Res. 2005 Jan;37(1):45-8.

6. Jiménez I, Sobrino T, Rodríguez-Yáñez M, et al. High serum levels of leptin are associated with post-stroke depression. Psychol Med. 2009 Jul;39(7):1201-9.

7. Jow GM, Yang TT, Chen CL. Leptin and cholesterol levels are low in major depressive disorder, but high in schizophrenia. J Affect Disord. 2006 Jan;90(1):21-7.

8. Lu XY. The leptin hypothesis of depression: a potential link between mood disorders and obesity? Curr Opin Pharmacol. 2007 Dec;7(6):648-52.

9. Fragala MS, Kraemer WJ, Volek JS, et al. Influences of a dietary supplement in combination with an exercise and diet regimen on adipocytokines and adiposity in women who are overweight. Eur J Appl Physiol. 2009; 105:665-72.