Adenylyl cyclase inhibitory pathway is differentially modified in rat white and brown fat by high-energy diets

Kenan, Yusuf; Levinson, Martha; Pines, Mark; Naim, Michael

doi:10.1152/ajpendo.1997.272.6.e1043

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…The level of expression of G-proteins is sensitive to both the nutritional and hormonal states of the organism (24). Alterations in adenylyl cyclase activity in response to high-energy diets (42) as well as in hypothyroidism (43)(44)(45) have been reported. Furthermore, the mechanism of action disentangled here may be applied not only to lipid metabolism regulation, but also to glucose homeostasis and insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Leptin‐induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes

2001

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The aim of the present study was to gain insight into the signaling pathway used by leptin to stimulate lipolysis. The lipolytic rate of white adipocytes from sex-and age-matched lean (؉/؉) and fa/fa rats was determined in the absence or presence of leptin together with a number of agents acting at different levels of the signaling cascade. Leptin did not modify FSK-, dbcAMP-, and IBMX-stimulated lipolysis. Lipolysis can also be maximally stimulated by lowering media adenosine levels with adenosine deaminase (ADA), i.e., in the ligand-free state. Although ADA produced near maximal lipolysis in adipocytes of lean animals, only half of the maximal lipolytic rate (50.9؎3.2%) was achieved in fat cells from fa/fa rats (P‫.)4300.0؍‬ In adipocytes from lean animals preincubated with ADA, leptin caused a concentration-related stimulation of lipolysis (P‫.)1000.0؍‬ However, leptin had no effect on the lipolytic activity of adipocytes in the ligand-free state from fa/fa rats. The adenosine A 1 receptor agonist CPA effectively inhibited basal lipolysis in both lean and obese adipocytes (P‫1000.0؍‬ and P‫,0900.0؍‬ respectively). Leptin had no effect on the lipolytic rate of adipocytes isolated from fa/fa rats and preincubated with CPA. When adipocytes were incubated with the A 1 receptor antagonist DPCPX, a significant increase in glycerol release was observed in fa/fa fat cells (P‫,)900.0؍‬ whereas cells isolated from lean rats showed no differences to ADA-stimulated lipolysis. After pretreatment with PTX, which inactivates receptor-mediated G i function, adipocytes of obese rats became as responsive to the stimulatory actions of ISO as cells from lean rats (P‫0900.0؍‬ vs. ISO in fa/fa rats; P‫6142.0؍‬ vs. lean rats, respectively). PTX treatment of lean cells, however, did not alter their response to this lipolytic agent. It can be concluded that the lipolytic effect of leptin is located at the adenylate cyclase/G i proteins level and that leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes.-Frühbeck, G., Gómez-Ambrosi, J., Salvador, J. Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes. FASEB J. 15, 333-340 (2001)

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Section: Discussionmentioning

confidence: 99%

Leptin‐induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes

2001

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“…Such a study is important, since recent studies have indicated differential modi®cation of white-and brown-adipose-tissue glucose transport and intracellular signalling mechanisms by high-fat feeding. 36,37 We examined white adipose tissue from several depots in view of data demonstrating that individual depots subserve distinct physiological functions and may exhibit differential sensitivities to insulin (see for example, Refs 38 ± 41).…”

Section: Discussionmentioning

confidence: 99%

The impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in brown- and a range of white-adipose-tissue depots in vivo

Holness

Sugden

1999

Int J Obes

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OBJECTIVE: To determine: (a) whether active pyruvate dehydrogenase (PDH a ) activity in interscapular brown adipose tissue (IBAT) is acutely regulated by altered insulin status at euglycaemia; (b) the relationship between glucose uptakeaphosphorylation and PDH a activities in IBAT in vivo; and (c) the impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in IBAT in comparison with that exerted on various white adipose tissue depots. DESIGN: Rats were provided with either a standard diet (8% fat, 72% carbohydrate, by energy) or a diet moderately high in saturated fat (47%, by energy) and low in carbohydrate (33%, by energy) for four weeks. Rats were studied in the absorptive state, in the post-absorptive state or after 2.5 h euglycaemic hyperinsulinaemia. Tissues sampled included IBAT and four white adipose tissue depots, two abdominal (parametrial (PM) and perirenal (PR)) and two super®cial (subcutaneous (SC) and interscapular (IS)). MEASUREMENTS: Whole-body glucose disposal was estimated using [3-3 H]glucose. Glucose uptakeaphosphorylation in vivo was estimated using 2-deoxy[1-3 H]-D-glucose. Insulin action was evaluated using the euglycaemic-hyperinsulinaemic clamp technique. PDH a activity was assayed spectrophotometrically in freeze-clamped tissue extracts. PDH kinase (PDK) activities were assayed in mitochondrial extracts by rates of ATP-dependent PDH a inactivation. RESULTS: Whole-body glucose disposal was decreased by high-fat-feeding in the post-absorptive state (P`0.05) and during euglycaemic hyperinsulinaemia (P`0.01). Glucose transportaphosphorylation in IBAT was decreased by highfat feeding in the absorptive (P`0.001) and post-absorptive states (by 84%, P`0.05) and during steady-state euglycaemic hyperinsulinaemia (by 73%, P`0.001). IBAT PDH a activities were suppressed by high-fat feeding. Euglycaemic hyperinsulinaemia in post-absorptive control rats increased PDH a activities in IBAT (P`0.001) to values comparable to those found in the absorptive state. Although IBAT PDH a activities were increased by euglycaemic hyperinsulinaemia in post-absorptive high-fat-fed rats, they remained lower (by 55%; P`0.01) than those of controls. The failure of hyperinsulinaemia to normalise IBAT pyruvate dehydrogenase complex (PDHC) activities in high-fat-fed rats was associated with a stable 1.4-fold increase in IBAT PDK activity. High-fat feeding decreased glucose utilisation rates in the post-absorptive state in IS, but not in SC, PM or PR white adipose tissue depots. Euglycaemic hyperinsulinaemia signi®cantly increased glucose utilisation in three out of the four depots of the control rats, but did not elicit statistically-signi®cant changes in high-fat-fed rats. High-fat feeding in¯uenced PDH a activity in PR, but was without signi®cant effect on PDH a activity in PM, SC and IS. CONCLUSIONS: The results demonstrate that PDH a activity in the IBAT of rats maintained on standard diet responds to changes in insulin concentrations over the low physiological range, and that i...

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“…In experiments using fat cells from young pigs, it was shown that feeding these animals feeds with the addition of maize starch caused a distinct rise in lipogenesis stimulated by insulin (Smith et al, 1996). It was also observed that excess energy in food may contribute to a reduction in the amount of cAMP and restriction of lipolysis in fat cells (Kenan et al, 1997).…”

Section: Hormonal Regulationmentioning

confidence: 99%

The effect of diet on fat cell metabolism. A review

Kandulska

Szkudelski²

1998

J. Anim. Feed Sci.

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A brief review of processes occurring in fat cells is given and the regulatory effects of certain hormones and nutrients are presented.Fat cells are found in the white adipose tissue and store substantial amounts of triglycerides. The process through which triglycerides are formed in these cells is called lipogenesis and is stimulated by insulin. The opposite process, lipolysis, i.e. the degradation of triglycerides with the liberation of glycerol and free fatty acids into the circulation, is stimulated by glucagon and adrenaline. Many factors related to nutrition such as, for example, fasting, nutritional status, the carbohydrate level of the diet, amount and composition of fats in it, can modify these processes. The diet and its composi tion also have an important effect on brown adipose tissue.

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Adenylyl cyclase inhibitory pathway is differentially modified in rat white and brown fat by high-energy diets

Cited by 5 publications

References 23 publications

Leptin‐induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes

Leptin‐induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes

The impact of increased dietary lipid on the regulation of glucose uptake and oxidation by insulin in brown- and a range of white-adipose-tissue depots in vivo

The effect of diet on fat cell metabolism. A review

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