Leptin resistance develops spontaneously in mice during adult life in a tissue-specific manner. Consequences for hepatic steatosis

Stucchi, Paula; Guzmán‐Ruiz, Rocío; Gil‐Ortega, Marta; Merino, Beatriz; Somoza, Beatriz; Cano, Victoria; Castro, Javier de; Sevillano, Julio; Ramos, M. Teresa; Fernández-Alfonso, Marı́a S.; Ruiz‐Gayo, Mariano

doi:10.1016/j.biochi.2011.06.020

Cited by 24 publications

(20 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously shown 29,35 32-wk of HFD induced a 3-fold increase in plasma insulin ( Figure 1A; p<0.001) and a 2-fold increase in plasma leptin concentrations ( Figure 1B; p<0.01). However, plasma adiponectin levels were significantly lower ( Figure 1C; p<0.01) in HFD compared to controls.…”

Section: Physiological Variables and Plasma Parameters After 32-week Hfdsupporting

confidence: 84%

“…However, these rats show elevated blood pressure, which is a strong stimulus for vascular remodeling. In contrast, our DIO model does not exhibit hypertension 29 but is characterized by a progressive development of insulin resistance during the onset of obesity 35 . In accordance, hypertrophic outward remodeling has been found in type 2 diabetic db/db mice 37 and in obese humans 6 in the absence of hypertension.…”

Section: Discussionmentioning

confidence: 81%

See 1 more Smart Citation

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Gil‐Ortega

Martín-Ramos

Arribas

et al. 2016

Vascular Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Physiological Variables and Plasma Parameters After 32-week Hfdsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 81%

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Gil‐Ortega

Martín-Ramos

Arribas

et al. 2016

Vascular Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our study shows that leptin resistance develops in the HF hippocampus for the Akt but not for the STAT3 pathway. This selective desensitization of a downstream signaling pathway coupled to leptin receptors, which has been described previously by our group in peripheral tissues (32), suggests that the integrity of the STAT3 pathway would be necessary for leptin effects on hippocampus plasticity. Furthermore, obese rodents with dysfunctional leptin receptors display impaired LTP and LTD within the hippocampus (16,21).…”

Section: E399supporting

confidence: 74%

High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission

Valladolid‐Acebes¹,

Merino²,

Principato³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

120

View full text Add to dashboard Cite

Valladolid-Acebes I, Merino B, Principato A, Fole A, Barbas C, Lorenzo MP, García A, Del Olmo N, Ruiz-Gayo M, Cano V. High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission. Am J Physiol Endocrinol Metab 302: E396 -E402, 2012. First published November 22, 2011; doi:10.1152/ajpendo.00343.2011.-Obesity and high-fat (HF) diets have a deleterious impact on hippocampal function and lead to impaired synaptic plasticity and learning deficits. Because all of these processes need an adequate glutamatergic transmission, we have hypothesized that nutritional imbalance triggered by these diets might eventually concern glutamate (Glu) neural pathways within the hippocampus. Glu is withdrawn from excitatory synapses by specific uptake mechanisms involving neuronal (EAAT-3) and glial (GLT-1, GLAST) transporters, which regulate the time that synaptically released Glu remains in the extracellular space and, consequently, the duration and location of postsynaptic receptor activation. The goal of the present study was to evaluate in mouse hippocampus the effect of a short-term high-fat dietary treatment on 1) Glu uptake kinetics, 2) the density of Glu carriers and Glu-degrading enzymes, 3) the density of Glu receptor subunits, and 4) synaptic transmission and plasticity. Here, we show that HF diet triggers a 50% decrease of the Michaelis-Menten constant together with a 300% increase of the maximal velocity of the uptake process. Glial Glu carriers GLT-1 and GLAST were upregulated in HF mice (32 and 27%, respectively), whereas Glu-degrading enzymes glutamine synthase and GABA-decarboxilase appeared to be downregulated in these animals. In addition, HF diet hippocampus displayed diminished basal synaptic transmission and hindered NMDAinduced long-term depression (NMDA-LTD). This was coincident with a reduced density of the NR2B subunit of NMDA receptors. All of these results are compatible with the development of leptin resistance within the hippocampus. Our data show that HF diets upregulate mechanisms involved in Glu clearance and simultaneously impair Glu metabolism. Neurochemical changes occur concomitantly with impaired basal synaptic transmission and reduced NMDA-LTD. Taken together, our results suggest that HF diets trigger neurochemical changes, leading to a desensitization of NMDA receptors within the hippocampus, which might account for cognitive deficits. obesity; electrophysiology; learning; long-term depression; glutamate uptake; leptin resistance GLUTAMATE (Glu) uptake is a pivotal process regulating excitatory transmission within the central nervous system, and its efficacy accounts for the time that released Glu remains in the extracellular space and, consequently, the duration of postsynaptic receptor activation. Glu uptake is carried out by specific neuronal (EAAT-3) and glial (GLT-1, GLAST) transporters, which display dynamic processes aimed at improving Glu clearance under conditions leading to increased release of Glu (27, 34). Impairment of Glu uptake due to brain injury (24, 28...

show abstract

“…Elevated levels of leptin might also contribute to reduce adipose lipogenesis (27,29,30). In fact, recent studies from our group have demonstrated that adipose tissue maintains leptin responsiveness after 8 wk HF treatment (31).…”

Section: Discussionmentioning

confidence: 89%

Circadian Feeding Drive of Metabolic Activity in Adipose Tissue and not Hyperphagia Triggers Overweight in Mice: Is There a Role of the Pentose-Phosphate Pathway?

et al. 2012

Self Cite

View full text Add to dashboard Cite

High-fat (HF) diets trigger an increase in adipose tissue and body weight (BW) and disordered eating behavior. Our study deals with the hypothesis that circadian distribution of energy intake is more relevant for BW dynamics than diet composition. Four-week-old mice were exposed for 8 wk to a HF diet and compared with animals receiving control chow. HF mice progressively increased BW, decreased the amount of nocturnal (1800-0900 h) calories (energy or food intake) (30%) and increased diurnal (0900-1800 h) caloric intake (energy or food intake), although total daily intake was identical between groups. Animals were killed at 3-h intervals and plasma insulin, leptin, corticosterone, glucose, and fatty acid levels quantified. Adipose tissue was weighed, and enzymatic activities integral to the pentose phosphate pathway (PPP) assayed in lumbar adipose tissue. Phosphorylated AMP-dependent protein kinase and fatty acid synthase were quantified by Western blotting. In HF mice, there was a shift in the circadian oscillations of plasma parameters together with an inhibition of PPP activity and a decrease in phosphorylated AMP-dependent protein kinase and fatty acid synthase. In a second experiment, HF mice were forced to adhere to a circadian pattern of food intake similar to that in control animals. In this case, BW, adipose tissue, morning plasma parameters and PPP activity appeared to be normal. These data indicate that disordered feeding behavior can trigger BW gain independently of food composition and daily energy intake. Because PPP is the main source of reduced nicotinamide adenine dinucleotide phosphate, we suggest that PPP inhibition might be an early marker of adipose dysfunction in diet-induced obesity.

show abstract

Leptin resistance develops spontaneously in mice during adult life in a tissue-specific manner. Consequences for hepatic steatosis

Cited by 24 publications

References 22 publications

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

Arterial stiffness is associated with adipokine dysregulation in non-hypertensive obese mice

High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission

Circadian Feeding Drive of Metabolic Activity in Adipose Tissue and not Hyperphagia Triggers Overweight in Mice: Is There a Role of the Pentose-Phosphate Pathway?

Contact Info

Product

Resources

About