Zinc may be a mediator of leptin production in humans

doi:10.1016/S0024-3205(00)00541-5

Life Sciences

Volume 66, Issue 22, 21 April 2000, Pages 2143-2149

https://doi.org/10.1016/S0024-3205(00)00541-5 Get rights and content

Abstract

Obese individuals have hyperleptinemia and hypozincemia. Moreover, leptin and zinc have circadian changes in circulating concentrations. We investigated their possible interaction and examined whether a difference existed between obese men and their lean controls. The results indicated the pattern of circadian change in plasma zinc and leptin did not markedly differ between the obese subjects and the lean controls. However, the obese had higher leptin and lower zinc plasma values at each sampling time than did the lean controls. Because an inverse correlation was found in plasma values between zinc and leptin (r = −0.51, p = 0.012), we further determined the role zinc might play in leptin production by human subcutaneous adipose tissue from female donors. The in vitro study showed that zinc treatment (0.2 $mmol L$ ) significantly increased leptin production (142%), however, this increment did not surpass that by insulin (10 $nmol L$ ). The data of this study suggest an interactive connection between zinc and leptin.

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Anorexia nervosa (AN) is a severe illness with diverse aetiological and maintaining contributors including neurobiological, metabolic, psychological, and social determining factors. In addition to nutritional recovery, multiple psychological and pharmacological therapies and brain-based stimulations have been explored; however, existing treatments have limited efficacy. This paper outlines a neurobiological model of glutamatergic and γ-aminobutyric acid (GABA)-ergic dysfunction, exacerbated by chronic gut microbiome dysbiosis and zinc depletion at a brain and gut level. The gut microbiome is established early in development, and early exposure to stress and adversity contribute to gut microbial disturbance in AN, early dysregulation to glutamatergic and GABAergic networks, interoceptive impairment, and inhibited caloric harvest from food (e.g., zinc malabsorption, competition for zinc ions between gut bacteria and host). Zinc is a key part of glutamatergic and GABAergic networks, and also affects leptin and gut microbial function; systems dysregulated in AN. Low doses of ketamine in conjunction with zinc, could provide an efficacious combination to act on NMDA receptors and normalise glutamatergic, GABAergic and gut function in AN.
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Citation Excerpt :
Individuals with a deficiency of Zn tend to gain fat mass, because it plays a major role in energy metabolism and satiety control [28]. Zn regulates leptin levels, and consequently controls fat mass [29]. However, the influence of Zn supplementation upon leptin levels has not been fully clarified in the scientific literature [28].
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Fifty-one healthy postmenopausal women aged 44–76 years from the province of Granada (Spain) were divided into two groups (placebo and zinc) of 25 and 26 women, respectively. The zinc group was supplemented with 50 mg/day of zinc for 8 weeks. Nutrient intake assessment was performed by means of a 24 -h reminder. Zinc was determined by flame atomic absorption spectrophotometry. Vitamin D was analyzed by liquid chromatography - tandem mass spectrometry. Leptin was determined by enzyme immunoassay.
Zinc supplementation improved the initial vitamin D₃ status of the postmenopausal population (p = 0.049). Plasma levels of 25−OH-D₃ increased significantly after Zn supplementation in women with lower age at menopause (p = 0.045). Both intake and plasma zinc levels were inversely correlated to serum leptin levels (p = 0.044 and p = 0.033, respectively), being significantly lower in lower age at menopause (p < 0.001).
Zinc supplementation improved vitamin D₃ status and was associated to low leptin levels in the postmenopausal women of the study.
Effects of prepartum zinc-methionine supplementation on feed digestibility, rumen fermentation patterns, immunity status, and passive transfer of immunity in dairy cows
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The aim of this study was to determine the effects of prepartum supplementation of zinc-methionine (Zn-Met) on feed digestibility, rumen fermentation patterns, and immunity status in dams and passive immunity transfer in their calves. A randomized complete design was used in this study. Forty multiparous Holstein dairy cows in late pregnancy (60 d before the expected calving date) were blocked by parity (2.1 ± 0.3), body weight (651 ± 52 kg), and expected calving date, and randomly assigned to 1 of 4 treatments. Cows were supplemented with Zn as Zn-Met at 0, 20, 40, or 60 mg/kg of dry matter (DM) from 60 d before expected calving date to the calving day. Though the nutrient digestibility was not affected by Zn supplementation, DM intake, Zn digestibility, and Zn deposition increased linearly with increasing Zn-Met supplementation. Ruminal pH and molar proportion of individual volatile fatty acids were similar, whereas a linear decrease and increase were observed in ruminal ammonia and microbial crude protein concentration, respectively, with increasing Zn-Met supplementation. Maternal serum concentration of alkaline phosphatase, carboxypeptidase, Cu and Zn superoxide dismutase, and total antioxidant capacity were greater in cows supplemented with >40 mg of Zn/kg of DM compared with the control group. With increasing Zn-Met supplementation, maternal blood concentration of IL-1 decreased linearly, whereas IL-2 and IL-6 increased linearly, and no differences were observed in IL-4. Concentration of nonesterified fatty acids and β-hydroxybutyric acids in maternal blood was similar between treatments. No difference was observed in colostrum composition with increasing Zn-Met supplementation. Concentration of Zn and immunoglobulins (including IgA, IgG, and IgM) in maternal blood did not differ among treatments. However, Zn concentration in colostrum and blood of calves increased linearly. The concentration of IgA and IgM in colostrum increased linearly with increasing Zn-Met supplementation, whereas no differences in immunoglobulins were observed in calf blood. In conclusion, Zn supplementation as Zn-Met at 40 of mg/kg of DM may improve antioxidant activity of dam and potentially increase passive immunity transfer in calves.
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Citation Excerpt :
Numerous associations between Zn2+ and endocrine signalling in relation to energy metabolism have previously been established [96]. Notably, Zn2+ affects either production, secretion, or activity of glucagon [97], insulin [98], adiponectin [99], and leptin [22]. Particularly intriguing interactions in the context of FFA-Zn crosstalk have been identified for insulin and leptin.
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Zinc may be a mediator of leptin production in humans

Abstract

Am. J. Clin. Nutr.

J. Nutr.

Biochem. Biophys. Res. Commun.

J. Nutr. Biochem.

Nature

Nature

N. Engl. J. Med.

J. Clin. Invest.

Nature Med.

J. Clin. Endocrinol. Metab.

J. Neuroendocrinol.

J. Med.