Increased concentrations of proteins Gi1 and Gi2 in adipocytes from aged rats alter the sensitivity of adenylyl cyclase to inhibitory and stimulatory agonists

Green, Allan; Gasic, Slavisa; Milligan, Graeme; Dobias, Susan B.

doi:10.1016/0026-0495(95)90272-4

Cited by 7 publications

(4 citation statements)

References 16 publications

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“…The negative effect of G i on brown adipocytes has also been proposed before, and cold exposure has been shown to decrease G i expression in BAT [60]. More importantly, an age-related increase of inhibitory G-proteins has been reported in adipocytes of aged rats [61]. In summary, these findings suggest that aging may result in altered concentrations of different sphingolipid species, including ceramides and S1P, which may attenuate brown adipocyte formation and their metabolic function.…”

Section: Discussionsupporting

confidence: 71%

Identification of functional lipid metabolism biomarkers of brown adipose tissue aging

Gohlke

Zagoriy²,

Inostroza³

et al. 2019

Molecular Metabolism

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Objective Aging is accompanied by loss of brown adipocytes and a decline in their thermogenic potential, which may exacerbate the development of adiposity and other metabolic disorders. Presently, only limited evidence exists describing the molecular alterations leading to impaired brown adipogenesis with aging and the contribution of these processes to changes of systemic energy metabolism. Methods Samples of young and aged murine brown and white adipose tissue were used to compare age-related changes of brown adipogenic gene expression and thermogenesis-related lipid mobilization. To identify potential markers of brown adipose tissue aging, non-targeted proteomic and metabolomic as well as targeted lipid analyses were conducted on young and aged tissue samples. Subsequently, the effects of several candidate lipid classes on brown adipocyte function were examined. Results Corroborating previous reports of reduced expression of uncoupling protein-1, we observe impaired signaling required for lipid mobilization in aged brown fat after adrenergic stimulation. Omics analyses additionally confirm the age-related impairment of lipid homeostasis and reveal the accumulation of specific lipid classes, including certain sphingolipids, ceramides, and dolichols in aged brown fat. While ceramides as well as enzymes of dolichol metabolism inhibit brown adipogenesis, inhibition of sphingosine 1-phosphate receptor 2 induces brown adipocyte differentiation. Conclusions Our functional analyses show that changes in specific lipid species, as observed during aging, may contribute to reduced thermogenic potential. They thus uncover potential biomarkers of aging as well as molecular mechanisms that could contribute to the degradation of brown adipocytes, thereby providing potential treatment strategies of age-related metabolic conditions.

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Section: Discussionsupporting

confidence: 71%

Identification of functional lipid metabolism biomarkers of brown adipose tissue aging

Gohlke

Zagoriy²,

Inostroza³

et al. 2019

Molecular Metabolism

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“…For example, the down-regulation of Gsa accounts for the rat pulmonary b 2 -adrenoceptor desensitization (42) and an increase in the Gia makes adenylyl cyclase more sensitive to the inhibition by adenosine A1 receptor agonist and less sensitive to isoproterenol (43).…”

Section: Marcel Dekker Inc • 270 Madison Avenue • New York Ny 10016mentioning

confidence: 99%

Increased Renal Angiotensin II AT₁Receptor Function in Obese Zucker Rat

Becker

Umrani

Lokhandwala

et al. 2003

Clinical and Experimental Hypertension

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Angiotensin II (Ang II) via the activation of AT1 receptors and subsequent stimulation of the tubular sodium transporters increases sodium and water reabsorption in the proximal tubule. An enhanced tubular action of Ang II is implicated in obesity related hypertension; however, the mechanism of such a phenomenon is unknown. Present study was designed to determine the AT1 receptor numbers and function in the proximal tubule of obese and lean Zucker rats. Obese Zucker rats were hypertensive and hyperinsulinemic. The plasma renin activity was similar in the lean and obese rats. Angiotensin II stimulated the Na,H-exchanger (NHE) activity in the proximal tubule, but the stimulatory response was markedly greater in obese than in lean rats. Similarly, Ang II caused greater inhibition in cAMP accumulation in the proximal tubule of obese compared to lean rats. The (125I]sar-Ang II binding revealed a 100% increase in the AT1 receptor number in the brush border membrane (BBM) of obese compared to lean rats. The Western blot analysis revealed a 36-51% increase in the Gi(alpha)1 and Gi(alpha)3 in the BBM of obese compared to lean rats. We conclude that increases in the AT1 receptor number and abundance of the Gi(alpha) on BBM may be responsible for the enhanced signaling and subsequent greater stimulation of NHE by Ang II in proximal tubules of obese rats. The greater stimulation of NHE by Ang II may contribute to the increased tubular sodium reabsorption and to the hypertension in obese Zucker rats.

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“…The authors did not, however, ®nd age-related differences in adenosine receptors or adenylyl cyclase activity. This led them to propose that higher concentrations of G i1 and G i2 in older rats were likely to explain observed age effects on stimulated lipolysis (Green et al, 1995). Although it is dif®cult to extrapolate results obtained in rodents to humans, these studies provide insight into the sub-cellular basis for changes in lipolysis with age.…”

Section: Effects Of Age On the Recruitment Of Fat Substrates: In Vitrmentioning

confidence: 99%

Lipid metabolism in the elderly

2000

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Adiposity increases with age. The size of the adipose tissue mass is determined by the balance between the recruitment of lipid substrates (ie free fatty acids) from adipose tissue and their subsequent oxidation by respiring tissues. Thus, change in the liberation of free fatty acids from adipocytes, the capacity of respiring tissue to oxidize free fatty acids or a combination of both may contribute to the age-related increase in body fat. This review focuses on studies that have examined the effect of age on free fatty acid release and the capacity of respiring tissues to oxidize fat. In vitro studies have shown that hormonal and pharmacological stimulation of lipolysis diminished with age. Despite this cellular defect, however, in vivo studies suggest that fatty acids are recruited from adipose tissue in excess of the energy demands of the body in older individuals. The capacity of respiring tissues, in particular skeletal muscle, to oxidize fat declines with age. The age-related decrease in fat oxidation is related to a reduction in both the quantity and oxidative capacity of respiring tissue. Taken together, these results suggest that an age-related decrease in the capacity of respiring tissues to oxidize fat, rather than decreased free fatty acid release, is a more likely determinant of lipid imbalance and the age-related increase in adiposity. Interventions designed to increase the mass or oxidative capacity of respiring tissue, therefore, may be effective in counteracting the age-related reduction in fat oxidation. Descriptors: aging; lipid metabolism; free fatty acids; adipose tissue; fat-free mass

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Increased concentrations of proteins Gi1 and Gi2 in adipocytes from aged rats alter the sensitivity of adenylyl cyclase to inhibitory and stimulatory agonists

Cited by 7 publications

References 16 publications

Identification of functional lipid metabolism biomarkers of brown adipose tissue aging

Identification of functional lipid metabolism biomarkers of brown adipose tissue aging

Increased Renal Angiotensin II AT₁Receptor Function in Obese Zucker Rat

Lipid metabolism in the elderly

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Increased concentrations of proteins Gi1 and Gi2 in adipocytes from aged rats alter the sensitivity of adenylyl cyclase to inhibitory and stimulatory agonists

Cited by 7 publications

References 16 publications

Identification of functional lipid metabolism biomarkers of brown adipose tissue aging

Identification of functional lipid metabolism biomarkers of brown adipose tissue aging

Increased Renal Angiotensin II AT1Receptor Function in Obese Zucker Rat

Lipid metabolism in the elderly

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Increased Renal Angiotensin II AT₁Receptor Function in Obese Zucker Rat