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Updated: Feb 25, 2026
Manipulation of Rhythmic Food Intake in Mice Using a Custom-Made Feeding System
Published on: December 16, 2022
Altered circadian feeding behavior and improvement of metabolic syndrome in obese Tac1-deficient mice
C A Maguire1, S León1, R S Carroll1
1Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Background:
Metabolic function is regulated by the interplay of central and peripheral factors that ultimately regulate food intake (FI) and energy expenditure. The tachykinin substance P (SP) has been identified as a novel regulator of energy balance, however, the mechanisms underlying this effect are ill-defined and conflicting data regarding the role of SP on FI have been reported by different groups.
Objective:
To further characterize the metabolic role of the Tac1 gene products (SP and neurokinin A) in mice through a series of genetic, metabolic and behavioral studies in Tac1-deficient mice.
Results:
Tac1-/- mice are leaner than controls and display reduced FI and altered feeding circadian rhythm, supported by disrupted expression of the clock genes Cry1/2, Per1/2 in the suprachiasmatic nucleus, mediobasal hypothalamus (MBH) and liver, as well as increased proopiomelanocortin expression in the MBH. Tac1 ablation induced resistance to obesity, improved glucose tolerance, prevented insulin resistance under high-fat diet, increased activation of brown adipose tissue and improved hepatic steatosis. Moreover, deletion of Tac1 in ob/ob mice ameliorated body weight gain in females only but was sufficient to decrease fat and triglyceride content in the liver of males.
Conclusions:
These results provide further evidence that Tac1 controls circadian feeding behavior and metabolism in mice through mechanisms that involve the regulation of the melanocortin system. In addition, these studies suggest that the blockade of SP may offer a new method to treat metabolic syndrome.
Insights
Mice lacking the Tac1 gene exhibit reduced food intake and altered circadian rhythms, leading to leanness and improved metabolic health. Blocking substance P (SP) may offer a new therapeutic strategy for metabolic syndrome.
Area of Science:
- Neuroendocrinology
- Metabolic Regulation
- Circadian Biology
Background:
- Metabolic function relies on central and peripheral factors influencing food intake and energy expenditure.
- Substance P (SP) is a novel, yet poorly understood, regulator of energy balance with conflicting data on its role in food intake.
Purpose of the Study:
- To investigate the metabolic functions of Tac1 gene products, substance P (SP) and neurokinin A, in mice.
- To characterize the effects of Tac1 deficiency on metabolism and feeding behavior.
Main Methods:
- Genetic studies using Tac1-deficient mice (Tac1-/-).
- Metabolic assessments including body weight, glucose tolerance, and insulin resistance.
- Behavioral studies on feeding patterns and circadian rhythms.
- Analysis of gene expression in the suprachiasmatic nucleus, hypothalamus, and liver.
Main Results:
- Tac1-/- mice showed reduced food intake, leanness, and altered feeding circadian rhythms.
- Tac1 deficiency improved glucose tolerance, prevented diet-induced insulin resistance, and enhanced brown adipose tissue activation.
- Tac1 ablation in ob/ob mice partially ameliorated weight gain and reduced liver fat accumulation.
Conclusions:
- Tac1 plays a crucial role in regulating circadian feeding behavior and metabolism via the melanocortin system.
- Blocking substance P (SP) presents a potential therapeutic approach for metabolic syndrome.
