Ventromedial Hypothalamic Lesions and the Mobilization of Fatty Acids

Nishizawà, Yoshiki; Bray, George A.

doi:10.1172/jci108984

Cited by 129 publications

(29 citation statements)

References 38 publications

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“…These gastric erosions are similar to the gastric ulcers produced in restrained rats (30). In this latter groups of rats the turnover of NE in the stomach is increased, consistent with increased sympathetic stimulation (30 (33) and reduce the rise of dopamine beta hydroxylase during exercise (34). These observations are consistent with the autonomic hypothesis (35,36) for hypothalamic obesity, which suggests that ventromedial hypothalamic lesions producing obesity reduce the activity of the sympathetic nervous system.…”

Section: Resultssupporting

confidence: 77%

Lateral hypothalamic lesions and norepinephrine turnover in rats.

Yoshida¹,

Kemnitz²,

Bray³

1983

J. Clin. Invest.

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A B S T R A C T Animals with lateral hypothalamic lesions lost significantly more weight in the 18 h following this lesion than did sham-operated animals or rats with cerebral cortical lesions deprived of food for the same time period. In the acutely fasted sham-operated animals the turnover of norepinephrine in interscapular brown adipose tissue, heart, and pancreas was slowed but in fasted rats with lateral hypothalamic lesions norepinephrine turnover rates were three-to ninefold faster in all three organs. Exposure to the cold (4°C) significantly increased norepinephrine turnover in the interscapular brown adipose tissue, heart, and pancreas of fasted sham-operated rats, but did not further increase the rate of turnover in lateral hypothalamic-lesioned rats. Rats with lesions in the cerebral cortex responded in a fashion similar to that of the sham-operated animals. Gastric erosions and microhemorrhagic gastric mucosa were observed in five of six acutely fasted rats with lateral hypothalamic lesions whereas all sham-operated rats had a normal appearance of the stomach lining. Animals with lateral hypothalamic lesions made 3 wk earlier also showed an increased rate of norepinephrine turnover in the interscapular brown adipose tissue, heart, and pancreas following an 18 h fast. Rats with bilateral lesions in the paraventricular region of the hypothalamus, however, responded similarly to sham-operated animals with a reduction in the turnover in norepinephrine with fasting and an increase in norepinephrine turnover rate after cold exposure even with fasting. These data suggest that lateral hypothalamic lesions produce an acute increase in turnover of norepinephrine, and that this increased turnover persists for up to 3 wk.

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Section: Resultssupporting

confidence: 77%

Lateral hypothalamic lesions and norepinephrine turnover in rats.

Yoshida¹,

Kemnitz²,

Bray³

1983

J. Clin. Invest.

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“…Tests of this notion in vivo, however, do not support an important role of EPI in lipolysis. Specifically, despite adrenal demedullation removing the sole source of circulating EPI, lipid mobilization is unaffected by several stimuli known to stimulate lipolysis [e.g., glucoprivation (42) and electrical stimulation of the medial hypothalamus (43)], including SD-induced lipid mobilization in Siberian hamsters (44). Thus, EPI is not necessary for lipolysis.…”

Section: The Sd (Mel)-induced Decrease In Body Fat Is Via the Sns Innmentioning

confidence: 99%

Thematic review series: Adipocyte Biology. Sympathetic and sensory innervation of white adipose tissue

Bartness

Song

2007

Journal of Lipid Research

182

142

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During our study of the reversal of seasonal obesity in Siberian hamsters, we found an interaction between receptors for the pineal hormone melatonin and the sympathetic nervous system (SNS) outflow from brain to white adipose tissue (WAT). This ultimately led us and others to conclude that the SNS innervation of WAT is the primary initiator of lipid mobilization in these as well as other animals, including humans. There is strong neurochemical (norepinephrine turnover), neuroanatomical (viral tract tracing), and functional (sympathetic denervation-induced blockade of lipolysis) evidence for the role of the SNS in lipid mobilization. Recent findings suggest the presence of WAT sensory innervation based on strong neuroanatomical (viral tract tracing, immunohistochemical markers of sensory nerves) and suggestive functional (capsaicin sensory denervation-induced WAT growth) evidence, the latter implying a role in conveying adiposity information to the brain. By contrast, parasympathetic nervous system innervation of WAT is characterized by largely negative neuroanatomical evidence (viral tract tracing, immunohistochemical and biochemical markers of parasympathetic nerves). Functional evidence (intraneural stimulation and in situ microdialysis) for the role of the SNS innervation in lipid mobilization in human WAT is convincing, with some controversy regarding the level of sympathetic nerve activity in human obesity.-Bartness, T. J., and C. K. Song. Sympathetic and sensory innervation of white adipose tissue. J. Lipid Res. 2007. 48: 1655-1672. Supplementary key words obesityObesity is a disease of literally and figuratively enormous proportions (1, 2) and is an independent risk factor for type II diabetes, cardiovascular disease, stroke, and some cancers (3-5). Estimates of the mortality rate of overweight/obese individuals range from ?325,000 deaths per year (6) to as low as ?26,000 (7), making overweight/ obesity either the number two or number seven cause of death in adults in the United States, respectively. Considerable research effort has focused on determining the factors involved in the development of obesity in nonhuman animals; consequently, our understanding of these is substantial, but still far from complete. Somewhat surprisingly, less effort has focused on determining the factors involved in the reversal of obesity in nonhuman animals. We have contributed to these latter efforts by studying the reversal of a naturally occurring seasonal obesity in Siberian hamsters (Phodopus sungorus). In the process of conducting this work, we discovered the importance of the sympathetic nervous system (SNS) in lipid mobilization from white adipose tissue (WAT) as well as more recently realizing the possible importance of the sensory innervation of WAT. Several overviews of the role of the SNS in lipid mobilization were published recently (8-11). To give a better understanding of how we came to the realization that lipid mobilization occurs primarily through the sympathetic innervation of WAT, we will descri...

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“…Moreover, both electrical activity within the VMH and the rate of release of endogenous catecholamine neurotransmitters from this region are affected by nutritional state and by acute changes in circulating concentrations of insulin and glucose (7,8). In addition, diminished sympathetic activity after electrolytic destruction of the VMH has been inferred from studies of the lipolytic response to various stimuli, including fasting (9,10). These considerations, therefore, suggest a potential role for the VMH in the regulation of sympathetic activity by diet.…”

Section: Introductionmentioning

confidence: 99%