Early exposure to a cholinergic receptor blocking agent mitigates adult obesity and protects pancreatic islet function in male rats

We tested the hypothesis that attenuation of the circulating insulin level in rats during early life can provide sustained protection against diet-induced obesity and metabolic dysfunction in adulthood. Male Wistar rats received intraperitoneal scopolamine butylbromide (SB) during the first 12 days of suckling, whereas control rats received 0.9% saline injections. The animals were weaned on <i>day 21</i> and fed a normal chow diet. At 60 days of age, the control and SB groups were fed a normal chow diet (ND; 4.5% fat) or a high-fat diet (HF; 35% fat) until 90 days of age to induce obesity and metabolic dysfunction. Insulin secretion, food intake, and body weight were measured. Pancreatic islet function, autonomic nervous system function, and glucose homeostasis were evaluated at 90 days of age. During lactation, the plasma insulin concentration was significantly lower in the SB groups than in the control group. SB rats also exhibited reduced body weight. The HF diet resulted in obesity, glucose intolerance, insulin resistance, disruption of insulin secretion, and vagal hyperactivity in adult control rats. Remarkably, SB-treated rats fed the HF diet showed attenuated body weight and adiposity and did not develop diet-induced glucose/insulin imbalance. In addition, vagal activity and adequate pancreatic islet insulin secretion were preserved. Offspring exposed to SB during early life are provided with long-lasting protection against obesity and metabolic complications induced by an HF diet. An attenuated circulating insulin level in early life may have far-reaching consequences on metabolic programming.<b>NEW & NOTEWORTHY</b> High insulin levels during early life may lead to the late development of obesity and diabetes. We investigated whether attenuation of insulin levels by using an antimuscarinic agent could prevent diet-induced obesity and diabetes. Rats' early exposure to an antimuscarinic agent reduced insulin levels during the lactation period and promoted protection against obesity and metabolic dysfunctions. Independent of the programming mechanisms, insulin levels during early life may be a defining factor of health or diseases later in life.