Correlations of serum leptin and leptin resistance with depression and anxiety in patients with type 2 diabetes

Both, Emőke; Huţanu, Adina; Sular, Floredana; Roiban, Andrada Larisa

doi:10.1111/pcn.12922

Cited by 18 publications

(15 citation statements)

References 44 publications

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“…Moreover, leptin is an adipokine-derived hormone upregulation of which triggers anxiolytic phenotype in mice (67) and deficiency results in anxiogenic-like behavior (68,69). Plasma leptin levels are associated with the emotional state of individuals throughout the day (70) and serum leptin and leptin resistance correlated with anxiety symptoms in patients with type 2 diabetes (T2D) (71). Therefore, the augmented circulating leptin levels reported in TauKO and hTau mice ( Figure 1E) could be involved in the anxiogenic phenotype observed in these animals, probably as a consequence of leptin resistance following chronic hyperleptinemia.…”

Section: Discussionmentioning

confidence: 96%

Behavioral Abnormalities in Knockout and Humanized Tau Mice

et al. 2020

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Microtubule-associated protein tau assists in stabilizing microtubules and has been particularly implicated in Alzheimer's disease (AD). Given the importance of tau to AD pathogenesis and therapies, it is important to understand non-classic physiological functions for this protein inside and outside the central nervous system (CNS). Our group has previously shown that tau ablation triggers glucose intolerance and pancreatic dysfunction in mice, suggesting that tau plays a role in peripheral metabolic regulation. Little is known about the role of tau in anxiety. Moreover, inconsistent results have been generated regarding the effects of tau deletion in memory. Here, we characterize systemic insulin resistance, anxiety-related behavior and memory in 15 to 20 weeks old Wild-Type (WT), Tau knockout (TauKO) and a distinct hTau mouse model consisting of tau knockout expressing the longest isoform (2N4R) of a non-mutant WT human Tau protein under the prion promoter (hTau). Our findings demonstrate that tau deletion leads to anxiety-related behavior, impaired contextual and cued fear memory. The presence of a human Tau transgene did not ameliorate the phenotypes observed in animals lacking the mouse tau protein and it elicited impairments in learning, memory, and peripheral insulin sensitivity. Our results suggest that tau protein plays a role in memory and anxiety-related behavior. Our findings also indicate that previously unrecognized functions for tau protein may be a complicating factor in using animal models on the TauKO background. Understanding the link between tau pathophysiology and cognitive and metabolic alterations is of great importance to establish the complete contribution of tau protein to AD pathogenesis.

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Section: Discussionmentioning

confidence: 96%

Behavioral Abnormalities in Knockout and Humanized Tau Mice

et al. 2020

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“…An animal model of diabetes, the ob/ob mouse, is deficient in leptin and displays marked hyperglycemia, hyperphagia, hyperinsulinemia, and obesity (Garthwaite et al., 1980; Lindström, 2007). In patients with T2DM, there was a significant association between depression‐anxiety symptoms and increased serum leptin levels along with leptin resistance (Cernea et al., 2019). CUMS treatment in ob/ob mice induced depressive‐like behavior, compromised spatial memory, increased the levels of pro‐inflammatory cytokines (IL‐6, IL‐1β, TNF‐α), decreased anti‐inflammatory (IL‐4, IL‐10) cytokines, and downregulated PPAR‐γ expression in the hippocampus and prefrontal cortex (PFC) (Qin et al., 2020).…”

Section: Physiological Factors That Play Key Roles In the Comorbiditymentioning

confidence: 99%

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

Subba

Sandhir

Singh

et al. 2021

Eur J of Neuroscience

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Diabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic–pituitary–adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut–brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin‐sensitizing agents can help to manage the distressing condition. The possibility of glucagon‐like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.

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“…[86]. Other studies also show high levels of leptin which correlates with anxiety levels [87][88][89]. Leptin administration resulted in dose-dependent anxiety decrease [86,90].…”

Section: Fosmentioning

confidence: 91%

Role of PPARs in Progression of Anxiety: Literature Analysis and Signaling Pathways Reconstruction

et al. 2020

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Peroxisome proliferator-activated receptor (PPAR) group includes three isoforms encoded by PPARG, PPARA, and PPARD genes. High concentrations of PPARs are found in parts of the brain linked to anxiety development, including hippocampus and amygdala. Among three PPAR isoforms, PPARG demonstrates the highest expression in CNS, where it can be found in neurons, astrocytes, and glial cells. Herein, the highest PPARG expression occurs in amygdala. However, little is known considering possible connections between PPARs and anxiety behavior. We reviewed possible connections between PPARs and anxiety. We used the Pathway Studio software (Elsevier). Signal pathways were created according to previously developed algorithms. SNEA was performed in Pathway Studio. Current study revealed 14 PPAR-regulated proteins linked to anxiety. Possible mechanism of PPAR involvement in neuroinflammation protection is proposed. Signal pathway reconstruction and reviewing aimed to reveal possible connection between PPARG and CCK-ergic system was conducted. Said analysis revealed that PPARG-dependent regulation of MME and ACE peptidase expression may affect levels of nonhydrolysed, i.e., active CCK-4. Impairments in PPARG regulation and following MME and ACE peptidase expression impairments in amygdala may be the possible mechanism leading to pathological anxiety development, with brain CCK-4 accumulation being a key link. Literature data analysis and signal pathway reconstruction and reviewing revealed two possible mechanisms of peroxisome proliferator-activated receptors involvement in pathological anxiety: (1) cytokine expression and neuroinflammation mechanism and (2) regulation of peptidases targeted to anxiety-associated neuropeptides, primarily CCK-4, mechanism.

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Correlations of serum leptin and leptin resistance with depression and anxiety in patients with type 2 diabetes

Abstract: Aim: The associations of serum leptin/soluble leptin receptor (sObR) and leptin resistance with symptoms of depression and anxiety were investigated in patients with type 2 diabetes (T2D).

Cited by 18 publications

References 44 publications

Behavioral Abnormalities in Knockout and Humanized Tau Mice

Behavioral Abnormalities in Knockout and Humanized Tau Mice

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control

Role of PPARs in Progression of Anxiety: Literature Analysis and Signaling Pathways Reconstruction

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