Histidine supplementation suppresses food intake and fat accumulation in rats

doi:10.1016/j.nut.2004.08.006

Nutrition

Volume 20, Issues 11–12, November–December 2004, Pages 991-996

https://doi.org/10.1016/j.nut.2004.08.006 Get rights and content

Abstract

Objective

Histamine, a derivative of histidine, decreases food intake and body fat by activation of histamine neurons. Our objective was to clarify the effect of dietary histidine, in particular, on food intake and/or body fat accumulation in rats.

Methods

Male Wistar rats were assigned to one of four groups after acclimation and allowed free access to diets containing 20% casein (0% histidine), 20% casein plus 1.0% histidine, 20% casein plus 2.5% histidine, or 20% casein plus 5% histidine for 8 d.

Results

Food intake and body weight were recorded daily and compared between groups. During the experimental period, food intake decreased according to the increases in dietary histidine. There was a negative and significant (P < 0.01) correlation between dietary histidine (grams per 8 d) and retroperitoneal fat pad (grams per 100 g of body weight). Uncoupling protein-1 mRNA in brown adipose tissue increased with increases in dietary histidine.

Conclusion

Our results indicate that dietary histidine suppresses food intake and fat accumulation in rats.

Introduction

Obesity, a common metabolic disorder characterized by a long-term imbalance between energy intake and expenditure, is a serious risk factor for lifestyle-related diseases such as type 2 diabetes, coronary artery disease, hypertension, and hyperlipidemia [1]. Although the pathophysiology underlying obesity is poorly understood, overeating is likely one of the most important factors. Thus, suppression of food intake might be effective in the prevention and/or treatment of obesity. There are many substances that suppress food intake and histamine is one of these. Sakata et al. reported that depletion of neuronal histamine in the hypothalamus mimics the abnormalities of obese Zucker rats [2], [3] and that grafting of fetal hypothalamus of lean Zucker littermates to obese rats attenuates almost all of the abnormalities [4]. In addition, Masaki et al. [5] reported that the histamine neuron system suppresses fat accumulation by upregulating mRNA expression of uncoupling protein (UCP), which expands energy consumption in rats. Fulop et al. [6] examined mice that had a targeted disruption of the key enzyme in histamine biosynthesis and reported that these mice were attenuated in their ability to induce UCP-1 mRNA in brown adipose tissue and that the mice showed remarkable increases in serum leptin, a signal to the brain that concerns energy homeostasis [7], [8], [9], [10]. These authors speculated that these metabolic changes were due to the impaired regulatory loop between leptin and hypothalamic histamine. From these results, it is likely that hypothalamic histamine plays a role in downstream signaling of leptin. Histamine is presumably the leading candidate for an antiobesity drug. However, histamine in the periphery cannot cross the blood–brain barrier [11]. Oral administration of histamine might not be useful for the prevention and/or treatment of obesity.

Histidine, a precursor for the synthesis of histamine, is an essential amino acid and is abundant in red meat and fish such as tuna and bonito. Our previous study in Japanese participants showed a negative and significant correlation between energy intake and histidine per protein intake [12], [13]. Thus, dietary histidine might suppress appetite by activating histamine neurons. In this regard, dietary histidine might be useful for the prevention of obesity.

In the present study, we examined the effect of dietary histidine on food intake, adiposity, and UCP mRNA expression in rats.

Section snippets

Experimental procedures

Five-week-old male Wistar rats (n = 24) were purchased from CLEA Japan (Tokyo, Japan). The animals were housed in individual stainless steel cages with wire mesh bottoms in a temperature- (23 ± 2°C) and light-controlled room (lights on from 8:00 am to 8:00 pm). To acclimate the rats to the experimental conditions, they were first given free access to a commercial diet (CE-2, CLEA Japan) for 7 d. After adaptation to this diet, the rats were assigned to one of four groups (n = 6/group) on the

Results

Rats' food intake decreased according to the amounts of dietary histidine provided (Figure 1). Compared with that in the 0% histidine group, food intake was significantly low in the 5% histidine group on each day and in the 2.5% histidine group on days 4 to 6 and 8. Food intake was slightly but not significantly less in rats fed the 1% histidine diet than in rats fed the 0% histidine diet on days 4 to 6. Total food intake decreased with increased dietary histidine (Table 2). Compared with the

Discussion

Food intake decreased with increased dietary histidine in this study (Table 1, Figure 1). Schwartz et al. [21] reported that brain histamine increases in rats after intraperitoneal administration of histidine. Yoshimatsu et al. [22] reported that intraperitoneal administration of histidine accelerates lipolysis the same as infusion of histamine into brain in rats. Histidine decarboxylase, an enzyme that converts histidine to histamine, is found in the hypothalamus [23]. Further, we previously

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Basic nutritional investigationHistidine supplementation suppresses food intake and fat accumulation in rats

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Experimental procedures

Results

Discussion

Nutrition

Biochem Biophys Res Commun

Comp Biochem Physiol C Toxicol Pharmacol

Lancet

Biochem Biophys Res Commun

Am J Clin Nutr

The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension

Arch Intern Med

Hypothalamic neuronal histamine modulate physiological responses induced by interleukin-1 B

Am J Physiol

Transplantation of lean fetal hypothalamus restores hypothalamic function in Zucker obese rats

Am J Physiol

Central infusion of histamine reduces fat accumulation and upregulates UCP family in leptin-resistant obese mice

Diabetes

Hyperleptinemia, visceral adiposity, and decreased glucose tolerance in mice with a targeted disruption of the histidine decarboxylase gene

Endocrinology

Positional cloning of the mouse obese gene and its human homologue

Nature

Weight-reducing effects of the plasma protein encoded by the obese gene

Science

Effects of the obese gene product on body weight regulation in obob mice

Science

Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks

Science

Histamine formation in rat brain during development

J Neurochem

Suppression of food intake by histidine-rich protein under low energy intake

J Jpn Soc Nutr Food Sci

Correlation between energy and histidine intake in female living in Setouchi area

J Jpn Soc Stud Obes

Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies

J Nutr

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

Basic nutritional investigation
Histidine supplementation suppresses food intake and fat accumulation in rats