Heat production and body weight changes following lateral hypothalamic lesions

Keesey, Richard E.; Corbett, Stephen W.; Hirvonen, Matt D.; Kaufman, Laryssa N.

doi:10.1016/0031-9384(84)90146-x

Cited by 27 publications

(3 citation statements)

References 27 publications

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“…The projection of EP3 receptor‐expressing neurons to the LH could mediate other PGE 2 functions that were not examined in the present study. The LH is involved in the regulation of food intake: lesions in the LH produced a profound anorexia (Keesey et al ., 1984). Endotoxin administration induces anorexia as well as fever with mechanisms dependent on PG production (Lugarini et al ., 2002), and these responses are at least partly dissociable events: anorexia associated with the acute‐phase response to acute inflammation is not secondary to fever (Larson et al ., 1996).…”

Section: Discussionmentioning

confidence: 99%

Direct pyrogenic input from prostaglandin EP3 receptor‐expressing preoptic neurons to the dorsomedial hypothalamus

Nakamura

Matsumura

et al. 2005

Eur J of Neuroscience

151

228

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Fever is induced by a neuronal mechanism in the brain. Prostaglandin (PG) E2 acts as a pyrogenic mediator in the preoptic area (POA) probably through the EP3 subtype of PGE receptor expressed on GABAergic neurons, and this PGE2 action triggers neuronal pathways for sympathetic thermogenesis in peripheral effector organs including brown adipose tissue (BAT). To explore pyrogenic efferent pathways from the POA, we determined projection targets of EP3 receptor-expressing POA neurons with a special focus on rat hypothalamic regions including the dorsomedial hypothalamic nucleus (DMH), which is known as a center for autonomic responses to stress. Among injections of cholera toxin b-subunit (CTb), a retrograde tracer, into hypothalamic regions at the rostrocaudal level of the DMH, injections into the DMH, lateral hypothalamic area (LH) and dorsal hypothalamic area (DH) resulted in EP3 receptor immunolabelling in substantial populations of CTb-labeled neurons in the POA. Bilateral microinjections of muscimol, a GABA(A) receptor agonist, into the DMH and a ventral region of the DH, but not those into the LH, inhibited thermogenic (BAT sympathetic nerve activity, BAT temperature, core body temperature and expired CO2) and cardiovascular (arterial pressure and heart rate) responses to an intra-POA PGE2 microinjection. Further immunohistochemical observations revealed a close association of POA-derived GABAergic axon swellings with DMH neurons projecting to the medullary raphe regions where sympathetic premotor neurons for febrile and thermoregulatory responses are localized. These results suggest that a direct projection of EP3 receptor-expressing POA neurons to the DMH/DH region mediates febrile responses via a GABAergic mechanism.

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Section: Discussionmentioning

confidence: 99%

Direct pyrogenic input from prostaglandin EP3 receptor‐expressing preoptic neurons to the dorsomedial hypothalamus

Nakamura

Matsumura

et al. 2005

Eur J of Neuroscience

151

228

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“…Similar results have been reported for weight loss after lesions of the lateral hypothalamus. Rats that have been weight reduced have a lower energy expenditure (18) and lose less weight than ad libitum-fed animals so that both groups of lesioned animals reach the same postlesion weight (17). Other investigators (20,21) have shown that the metabolic response to acute inflammation caused by turpentine injection is also related to the energy status of the rats at the time of injection.…”

Section: Discussionmentioning

confidence: 99%

Weight loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status

Harris

Mitchell

Simpson

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

114

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Acute release of corticotropin-releasing factor (CRF) during repeated restraint (3-h restraint on each of 3 days) causes temporary hypophagia but chronic suppression of body weight in rats. Here we demonstrated that a second bout of repeated restraint caused additional weight loss, but continuing restraint daily for 10 days did not increase weight loss because the rats adapted to the stress. In these two studies serum leptin, which suppresses the endocrine response to stress, was reduced in restrained rats. Peripheral infusion of leptin before and during restraint did not prevent stress-induced weight loss, although stress-induced corticosterone release was suppressed. Restrained rats were hyperthermic during restraint, but there was no evidence that fever or elevated free interleukin-6 caused the sustained reduction in weight. Restraining food-restricted rats caused a small but significant weight loss. Food-restricted rats fed ad libitum after the end of restraint showed a blunted hyperphagia and slower rate of weight regain than their controls. These results indicate that repeated acute stress induces a chronic change in weight independent of stress-induced hypophagia and may represent a change in homeostasis initiated by repeated acute activation of the central CRF system.

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“…The rationale for the selected targets is based on early experimental studies during the 1940s and 1950s that displayed the hypothalamic role in feeding behavior [53][54][55], classifying the VMH as the "Satiety center" and the LH as the "appetite center." A decrease in food intake, weight loss, and an increased metabolic rate were seen after ablative lesions on the LH [18,[56][57][58], resulting in eventual weight loss from varying degrees of aphagia and increased heat production [59]. In 2007, Sani et al [19] replicated the ablative effects by performing high-frequency neurostimulation (180-200 Hz) in the LH in a rodent model, which showed weight loss despite no difference in diets among groups; nonetheless, reports from Schallert et al [60] showed that low-frequency stimulation (<100 Hz) of the same target resulted in increased food intake and food hoarding, which suggests that a single target might have the potential to produce either weight gain and loss, depending on the stimulation parameters used.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Deep Brain Stimulation in Reducing Body Mass Index and Weight: A Systematic Review

López

Navarro

Crispín

2021

Stereotact Funct Neurosurg

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Background: Obesity has become a major public health concern worldwide, with current behavioral, pharmacological, and surgical treatments offering varying rates of success and adverse effects. Neurosurgical approaches to treatment of refractory obesity include deep brain stimulation (DBS) on either specific hypothalamic or reward circuitry nuclei, which might contribute to weight reduction through different mechanisms. We aimed to determine the safety and clinical effect of DBS in medical refractory obesity. Summary: Adhering to PRISMA guidelines, we performed a systematic review to identify all original studies – observational and experimental – in which DBS was performed to treat refractory obesity. From database inception to April 2021, we conducted our search in PubMed, Scopus, and LILACS databases using the following MeSH terms: “Obesity” OR “Prader-Willi Syndrome” AND “Deep Brain Stimulation.” The main outcomes were safety and weight loss measured with the body mass index (BMI). The Grading of Recommendations Assessment, Development, and Evaluation methods were applied to evaluate the quality of evidence. This study protocol was registered with PROSPERO ID: CRD42019132929. Seven studies involving 12 patients met the inclusion criteria; the DBS target was the nucleus accumbens in four (57.1%), the lateral hypothalamic area in two (29.6%), and the ventral hypothalamus in one (14.3%). Further, 33% of participants had obesity secondary to Prader-Willi syndrome (PWS) and 66.6% had primary obesity. The global BMI average at baseline was 46.7 (SD: 9.6, range: 32.2–59.1), and after DBS, 42.8 (SD: 8.8, range: 25–53.9), with a mean difference of 3.9; however, the delta in PWS patients was −2.3 and 10 in those with primary obesity. The incidence of moderate side effects was 33% and included manic symptoms (N = 2), electrode fracture (N = 1), and seizure (N = 1); mild complications (41.6%) included skin infection (N = 2), difficulties falling asleep (N = 1), nausea (N = 1), and anxiety (N = 1). Key Messages: Despite available small case series and case reports reporting a benefit in the treatment of refractory obesity with DBS, this study emphasizes the need for prospective studies with longer follow-ups in order to further address the efficacy and indications.

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Heat production and body weight changes following lateral hypothalamic lesions

Cited by 27 publications

References 27 publications

Direct pyrogenic input from prostaglandin EP3 receptor‐expressing preoptic neurons to the dorsomedial hypothalamus

Direct pyrogenic input from prostaglandin EP3 receptor‐expressing preoptic neurons to the dorsomedial hypothalamus

Weight loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status

Effectiveness of Deep Brain Stimulation in Reducing Body Mass Index and Weight: A Systematic Review

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