Obesity and the Regulation of Body Mass:- Leptin Stimulates Production of Anorexigenic Peptide Hormones
Two types of neurons in the arcuate nucleus control fuel intake and metabolism (Fig. 1). The orexigenic (appetite-stimulating) neurons stimulate eating by producing and releasing neuropeptide Y (NPY), which causes the next neuron in the circuit to send the signal to the brain, Eat! The blood level of NPY rises during starvation, and is elevated in both ob/ob and db/db mice. The high NPY concentration presumably underlies the obesity of these mice, who eat voraciously.
FIGURE 1 Hormones that control eating. In the arcuate nucleus, two sets of neurosecretory cells receive hormonal input and relay neuronal signals to the cells of muscle, adipose tissue, and liver. Leptin and insulin are released from adipose tissue and pancreas, respectively, in proportion to the mass of body fat. The two hormones act on anorexigenic neurosecretory cells (red) to trigger release of -MSH; this produces neuronal signals to eat less and metabolize more fuel. Leptin and insulin also act on orexigenic neurosecretory cells (green) to inhibit the release of NPY, reducing the “eat” signal sent to the tis sues. As described later in the text, the gastric hormone ghrelin stimulates appetite by activating the NPY-expressing cells; , released from the colon, inhibits these neurons and thereby decreases appetite. Each of the two types of neurosecretory cells inhibits hormone production by the other, so any stimulus that activates orexigenic cells inactivates anorexigenic cells, and vice versa. This strengthens the effect of stimulatory inputs.
The anorexigenic (appetite-suppressing) neurons in the arcuate nucleus produce -melanocyte-stimulating hormone (α-MSH), formed from its polypeptide pre cursor pro-opiomelanocortin . Release of α-MSH causes the next neuron in the circuit to send the signal to the brain, Stop eating! The amount of leptin released by adipose tissue de pends on both the number and the size of adipocytes. When weight loss decreases the mass of lipid tissue, leptin levels in the blood decrease, the production of NPY is diminished, and the processes in adipose tissue shown in Figure 1 are reversed. Uncoupling is diminished, slowing thermogenesis and saving fuel, and fat mobilization slows in response to reduced signaling by cAMP. Consumption of more food combined with more efficient utilization of fuel results in replenishment of the fat reserve in adipose, bringing the system back into balance.
